{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:24:32Z","timestamp":1790227472333,"version":"4.1.0"},"reference-count":208,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T00:00:00Z","timestamp":1564444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente Ospedale Pediatrico Bambino Ges\u00f9","award":["none"],"award-info":[{"award-number":["none"]}]},{"name":"Ricerca Finalizzata from Italian Ministry of Health","award":["RF-2016-02363642"],"award-info":[{"award-number":["RF-2016-02363642"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin\/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus\u2019s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases.<\/jats:p>","DOI":"10.3390\/ijms20153715","type":"journal-article","created":{"date-parts":[[2019,7,30]],"date-time":"2019-07-30T11:15:56Z","timestamp":1564485356000},"page":"3715","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5014-430X","authenticated-orcid":false,"given":"Loredana","family":"Cifaldi","sequence":"first","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5533-0304","authenticated-orcid":false,"given":"Margherita","family":"Doria","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Zicari","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Cancrini","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-4719","authenticated-orcid":false,"given":"Paolo","family":"Palma","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Rossi","sequence":"additional","affiliation":[{"name":"Academic Department of Pediatrics, Research Unit of Congenital and Perinatal Infection, Bambino Ges\u00f9 Children\u2019s Hospital, 00165 Rome, Italy"},{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1182\/blood-2007-09-077438","article-title":"Human natural killer cells","volume":"112","author":"Caligiuri","year":"2008","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/ni1582","article-title":"Functions of natural killer cells","volume":"9","author":"Vivier","year":"2008","journal-title":"Nat. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/icb.2010.78","article-title":"Activating and inhibitory receptors of natural killer cells","volume":"89","author":"Pegram","year":"2011","journal-title":"Immunol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1038\/nri3799","article-title":"Balancing natural killer cell activation through paired receptors","volume":"15","author":"Martinet","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.4049\/jimmunol.171.9.4473","article-title":"Virus evasion of mhc class i molecule presentation","volume":"171","author":"Petersen","year":"2003","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.cell.2017.11.037","article-title":"Natural killer cells control tumor growth by sensing a growth factor","volume":"172","author":"Barrow","year":"2018","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1126\/science.1258867","article-title":"Antitumor immunity. A shed nkg2d ligand that promotes natural killer cell activation and tumor rejection","volume":"348","author":"Deng","year":"2015","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/nature01112","article-title":"Tumour-derived soluble mic ligands impair expression of nkg2d and t-cell activation","volume":"419","author":"Groh","year":"2002","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.it.2013.01.003","article-title":"Activating natural cytotoxicity receptors of natural killer cells in cancer and infection","volume":"34","author":"Koch","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1159\/000327014","article-title":"Mechanisms of tumor and viral immune escape from natural killer cell-mediated surveillance","volume":"3","author":"Groth","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e609","DOI":"10.1016\/S2214-109X(16)30143-7","article-title":"Global burden of cancers attributable to infections in 2012: A synthetic analysis","volume":"4","author":"Plummer","year":"2016","journal-title":"Lancet. Glob Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.coi.2007.11.002","article-title":"Immune evasion of natural killer cells by viruses","volume":"20","author":"Jonjic","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Ma, Y., Li, X., and Kuang, E. (2016). Viral evasion of natural killer cell activation. Viruses, 8.","DOI":"10.3390\/v8040095"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nri1199","article-title":"Roles of the nkg2d immunoreceptor and its ligands","volume":"3","author":"Raulet","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1084\/jem.20030788","article-title":"Identification of pvr (cd155) and nectin-2 (cd112) as cell surface ligands for the human dnam-1 (cd226) activating molecule","volume":"198","author":"Bottino","year":"2003","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1146\/annurev.immunol.19.1.197","article-title":"Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis","volume":"19","author":"Moretta","year":"2001","journal-title":"Annu Rev. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.immunol.20.092501.134942","article-title":"Kir: Diverse, rapidly evolving receptors of innate and adaptive immunity","volume":"20","author":"Vilches","year":"2002","journal-title":"Annu Rev. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1084\/jem.188.12.2375","article-title":"Natural killer (nk) cell-mediated cytotoxicity: Differential use of trail and fas ligand by immature and mature primary human nk cells","volume":"188","author":"Zamai","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.3389\/fimmu.2018.02041","article-title":"Targeting checkpoint receptors and molecules for therapeutic modulation of natural killer cells","volume":"9","author":"Kim","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.semcancer.2006.07.002","article-title":"The role of nk cell recognition of nectin and nectin-like proteins in tumor immunosurveillance","volume":"16","author":"Fuchs","year":"2006","journal-title":"Semin Cancer Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/eji.200940234","article-title":"Loss of dnam-1 contributes to cd8+ t-cell exhaustion in chronic hiv-1 infection","volume":"40","author":"Cella","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.virol.2012.04.006","article-title":"Cd8 t cell defect of tnf-alpha and il-2 in dnam-1 deficient mice delays clearance in vivo of a persistent virus infection","volume":"429","author":"Welch","year":"2012","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.immuni.2013.12.011","article-title":"Costimulatory molecule dnam-1 is essential for optimal differentiation of memory natural killer cells during mouse cytomegalovirus infection","volume":"40","author":"Nabekura","year":"2014","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/icb.2013.95","article-title":"Dnam-1 control of natural killer cells functions through nectin and nectin-like proteins","volume":"92","author":"Smyth","year":"2014","journal-title":"Immunol. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8109","DOI":"10.1038\/ncomms9109","article-title":"\u2018Emergency exit\u2019 of bone-marrow-resident cd34(+)dnam-1(bright)cxcr4(+)-committed lymphoid precursors during chronic infection and inflammation","volume":"6","author":"Bozzano","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1189\/jlb.1208745","article-title":"Heterogeneous expression of the adhesion receptor cd226 on murine nk and t cells and its function in nk-mediated killing of immature dendritic cells","volume":"86","author":"Seth","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.celrep.2015.03.006","article-title":"Dnam-1 expression marks an alternative program of nk cell maturation","volume":"11","author":"Martinet","year":"2015","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/intimm\/dxh059","article-title":"Functional characterization of dnam-1 (cd226) interaction with its ligands pvr (cd155) and nectin-2 (prr-2\/cd112)","volume":"16","author":"Shibuya","year":"2004","journal-title":"Int. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/imm.12516","article-title":"Critical roles of co-activation receptor dnax accessory molecule-1 in natural killer cell immunity","volume":"146","author":"Xiong","year":"2015","journal-title":"Immunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1007\/s00262-009-0682-y","article-title":"Expression of adhesion molecules and ligands for activating and costimulatory receptors involved in cell-mediated cytotoxicity in a large panel of human melanoma cell lines","volume":"58","author":"Casado","year":"2009","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9180","DOI":"10.1158\/0008-5472.CAN-04-2682","article-title":"Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: Critical role of dnax accessory molecule-1-poliovirus receptor interaction","volume":"64","author":"Castriconi","year":"2004","journal-title":"Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1111\/cas.13324","article-title":"Cd155, an onco-immunologic molecule in human tumors","volume":"108","author":"Gao","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1182\/blood-2005-04-1684","article-title":"Tumor rejection by the poliovirus receptor family ligands of the dnam-1 (cd226) receptor","volume":"107","author":"Shibuya","year":"2006","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1476-4598-12-60","article-title":"Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers","volume":"12","author":"Oshima","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1242\/jcs.159400","article-title":"Connections matter--how viruses use cell-cell adhesion components","volume":"128","author":"Mateo","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1172\/JCI36022","article-title":"Ncrs and dnam-1 mediate nk cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo","volume":"119","author":"Lakshmikanth","year":"2009","journal-title":"J. Clin Invest."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e1338994","DOI":"10.1080\/2162402X.2017.1338994","article-title":"Cd226(-\/-) natural killer cells fail to establish stable contacts with cancer cells and show impaired control of tumor metastasis in vivo","volume":"6","author":"Kim","year":"2017","journal-title":"Oncoimmunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"902","DOI":"10.4049\/jimmunol.0903225","article-title":"Dnam-1\/cd155 interactions promote cytokine and nk cell-mediated suppression of poorly immunogenic melanoma metastases","volume":"184","author":"Chan","year":"2010","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1084\/jem.20150792","article-title":"Dnam-1 controls nk cell activation via an itt-like motif","volume":"212","author":"Zhang","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1084\/jem.20081752","article-title":"Dnam-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors","volume":"205","author":"Gilfillan","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nrm2457","article-title":"Nectins and nectin-like molecules: Roles in contact inhibition of cell movement and proliferation","volume":"9","author":"Takai","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S1074-7613(00)70060-4","article-title":"Dnam-1, a novel adhesion molecule involved in the cytolytic function of t lymphocytes","volume":"4","author":"Shibuya","year":"1996","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S1074-7613(00)80136-3","article-title":"Physical and functional association of lfa-1 with dnam-1 adhesion molecule","volume":"11","author":"Shibuya","year":"1999","journal-title":"Immunity"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4518","DOI":"10.4049\/jimmunol.1401972","article-title":"Coordinated expression of dnam-1 and lfa-1 in educated nk cells","volume":"194","author":"Enqvist","year":"2015","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"E11731","DOI":"10.1073\/pnas.1814052115","article-title":"Cd226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor foxo1","volume":"115","author":"Du","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2015.02.006","article-title":"Transcription factor foxo1 is a negative regulator of natural killer cell maturation and function","volume":"42","author":"Deng","year":"2015","journal-title":"Immunity"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.3389\/fimmu.2018.01072","article-title":"Coming of age: Cd96 emerges as modulator of immune responses","volume":"9","author":"Georgiev","year":"2018","journal-title":"Front Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.it.2016.10.002","article-title":"Tigit: A key inhibitor of the cancer immunity cycle","volume":"38","author":"Manieri","year":"2017","journal-title":"Trends Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/s41590-018-0132-0","article-title":"Blockade of the checkpoint receptor tigit prevents nk cell exhaustion and elicits potent anti-tumor immunity","volume":"19","author":"Zhang","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/ni.2850","article-title":"The receptors cd96 and cd226 oppose each other in the regulation of natural killer cell functions","volume":"15","author":"Chan","year":"2014","journal-title":"Nat. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Holmes, V.M., Maluquer de Motes, C., Richards, P.T., Roldan, J., Bhargava, A.K., Orange, J.S., and Krummenacher, C. (2019). Interaction between nectin-1 and the human natural killer cell receptor cd96. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212443"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.4049\/jimmunol.172.7.3994","article-title":"Cutting edge: Cd96 (tactile) promotes nk cell-target cell adhesion by interacting with the poliovirus receptor (cd155)","volume":"172","author":"Fuchs","year":"2004","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11413","DOI":"10.1074\/jbc.M117.786483","article-title":"Recognition of nectin-2 by the natural killer cell receptor t cell immunoglobulin and itim domain (tigit)","volume":"292","author":"Deuss","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"17858","DOI":"10.1073\/pnas.0903474106","article-title":"The interaction of tigit with pvr and pvrl2 inhibits human nk cell cytotoxicity","volume":"106","author":"Stanietsky","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.3389\/fimmu.2018.02341","article-title":"Expression of the inhibitory receptor tigit is up-regulated specifically on nk cells with cd226 activating receptor from hiv-infected individuals","volume":"9","author":"Yin","year":"2018","journal-title":"Front Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1242\/jcs.00167","article-title":"Nectin and afadin: Novel organizers of intercellular junctions","volume":"116","author":"Takai","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/nsmb.2366","article-title":"Nectin ectodomain structures reveal a canonical adhesive interface","volume":"19","author":"Harrison","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1042\/BCJ20160235","article-title":"Nectin spot: A novel type of nectin-mediated cell adhesion apparatus","volume":"473","author":"Mizutani","year":"2016","journal-title":"Biochem. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/bs.ctdb.2014.11.019","article-title":"Nectins and nectin-like molecules in development and disease","volume":"112","author":"Mandai","year":"2015","journal-title":"Curr. Top Dev. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/j.1349-7006.2003.tb01499.x","article-title":"Nectins and nectin-like molecules: Roles in cell adhesion, migration, and polarization","volume":"94","author":"Takai","year":"2003","journal-title":"Cancer Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.1182\/blood.V92.12.4602","article-title":"The human poliovirus receptor related 2 protein is a new hematopoietic\/endothelial homophilic adhesion molecule","volume":"92","author":"Lopez","year":"1998","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1128\/MCB.20.8.2865-2873.2000","article-title":"Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell-cell adherens junctions","volume":"20","author":"Bouchard","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1083\/jcb.200103113","article-title":"Nectin: An adhesion molecule involved in formation of synapses","volume":"156","author":"Mizoguchi","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/viro.1998.9218","article-title":"A cell surface protein with herpesvirus entry activity (hveb) confers susceptibility to infection by mutants of herpes simplex virus type 1, herpes simplex virus type 2, and pseudorabies virus","volume":"246","author":"Warner","year":"1998","journal-title":"Virology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"11185","DOI":"10.1128\/JVI.75.22.11185-11195.2001","article-title":"Structural features of nectin-2 (hveb) required for herpes simplex virus entry","volume":"75","author":"Martinez","year":"2001","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Son, Y., Lee, B., Choi, Y.J., Jeon, S.A., Kim, J.H., Lee, H.K., Kwon, S.M., and Cho, J.Y. (2016). Nectin-2 (cd112) is expressed on outgrowth endothelial cells and regulates cell proliferation and angiogenic function. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0163301"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1161\/HYPERTENSIONAHA.109.130443","article-title":"Deficiency of nectin-2 leads to cardiac fibrosis and dysfunction under chronic pressure overload","volume":"54","author":"Ueyama","year":"2009","journal-title":"Hypertension"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"43205","DOI":"10.1074\/jbc.M103810200","article-title":"Nectin4\/prr4, a new afadin-associated member of the nectin family that trans-interacts with nectin1\/prr1 through v domain interaction","volume":"276","author":"Reymond","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1084\/jem.20032206","article-title":"Dnam-1 and pvr regulate monocyte migration through endothelial junctions","volume":"199","author":"Reymond","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10930","DOI":"10.1158\/0008-5472.CAN-05-1890","article-title":"Cd155\/pvr enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics","volume":"65","author":"Sloan","year":"2005","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3503","DOI":"10.1182\/blood-2008-08-173914","article-title":"Atm-atr-dependent up-regulation of dnam-1 and nkg2d ligands on multiple myeloma cells by therapeutic agents results in enhanced nk-cell susceptibility and is associated with a senescent phenotype","volume":"113","author":"Soriani","year":"2009","journal-title":"Blood"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1182\/blood-2010-08-300954","article-title":"Dnam-1 ligand expression on ag-stimulated t lymphocytes is mediated by ros-dependent activation of DNA-damage response: Relevance for nk-t cell interaction","volume":"117","author":"Ardolino","year":"2011","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"178698","DOI":"10.1155\/2015\/178698","article-title":"Nkg2d and dnam-1 ligands: Molecular targets for nk cell-mediated immunotherapeutic intervention in multiple myeloma","volume":"2015","author":"Fionda","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1038\/sj.onc.1208409","article-title":"Transcriptional activation of the mouse necl-5\/tage4\/pvr\/cd155 gene by fibroblast growth factor or oncogenic ras through the raf-mek-erk-ap-1 pathway","volume":"24","author":"Hirota","year":"2005","journal-title":"Oncogene"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"25697","DOI":"10.1074\/jbc.M201378200","article-title":"Expression of the human poliovirus receptor\/cd155 gene is activated by sonic hedgehog","volume":"277","author":"Solecki","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/JID.2015.404","article-title":"Melanoma cells control antimelanoma ctl responses via interaction between tigit and cd155 in the effector phase","volume":"136","author":"Inozume","year":"2016","journal-title":"J. Invest. Dermatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.3389\/fimmu.2019.01231","article-title":"Spectrum of viral infections among primary immunodeficient children: Report from a national registry","volume":"10","author":"Essa","year":"2019","journal-title":"Front Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"S67","DOI":"10.1093\/infdis\/jiw217","article-title":"Cytomegalovirus and hiv: A dangerous pas de deux","volume":"214","author":"Gianella","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbmt.2014.11.002","article-title":"Recent advances in cytomegalovirus: An update on pharmacologic and cellular therapies","volume":"21","author":"Boeckh","year":"2015","journal-title":"Biol. Blood Marrow Transplant"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.immuni.2015.02.008","article-title":"Cytomegalovirus infection drives adaptive epigenetic diversification of nk cells with altered signaling and effector function","volume":"42","author":"Schlums","year":"2015","journal-title":"Immunity"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1126\/science.1070884","article-title":"Direct recognition of cytomegalovirus by activating and inhibitory nk cell receptors","volume":"296","author":"Arase","year":"2002","journal-title":"Science"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1182\/blood-2004-05-2058","article-title":"Imprint of human cytomegalovirus infection on the nk cell receptor repertoire","volume":"104","author":"Guma","year":"2004","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1084\/jem.20151899","article-title":"Inflammatory monocytes and nk cells play a crucial role in dnam-1-dependent control of cytomegalovirus infection","volume":"213","author":"Kaynan","year":"2016","journal-title":"J. Exp. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/S1074-7613(00)80349-0","article-title":"The er-luminal domain of the hcmv glycoprotein us6 inhibits peptide translocation by tap","volume":"6","author":"Ahn","year":"1997","journal-title":"Immunity"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11753","DOI":"10.1128\/JVI.76.22.11753-11756.2002","article-title":"The human cytomegalovirus us10 gene product delays trafficking of major histocompatibility complex class i molecules","volume":"76","author":"Furman","year":"2002","journal-title":"J. Virol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"11327","DOI":"10.1073\/pnas.93.21.11327","article-title":"Human cytomegalovirus us3 impairs transport and maturation of major histocompatibility complex class i heavy chains","volume":"93","author":"Jones","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1128\/JVI.80.2.951-963.2006","article-title":"Human cytomegalovirus protein pp71 disrupts major histocompatibility complex class i cell surface expression","volume":"80","author":"Trgovcich","year":"2006","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S1074-7613(01)00095-4","article-title":"Ulbps, novel mhc class i-related molecules, bind to cmv glycoprotein ul16 and stimulate nk cytotoxicity through the nkg2d receptor","volume":"14","author":"Cosman","year":"2001","journal-title":"Immunity"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1002\/1521-4141(200105)31:5<1428::AID-IMMU1428>3.0.CO;2-4","article-title":"Ulbp1, 2, 3: Novel mhc class i-related molecules that bind to human cytomegalovirus glycoprotein ul16, activate nk cells","volume":"31","author":"Kubin","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1002\/immu.200390022","article-title":"Selective intracellular retention of virally induced nkg2d ligands by the human cytomegalovirus ul16 glycoprotein","volume":"33","author":"Welte","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bbrc.2006.05.092","article-title":"Down-regulation of the nkg2d ligand mica by the human cytomegalovirus glycoprotein ul142","volume":"346","author":"Chalupny","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1126\/science.1140956","article-title":"Host immune system gene targeting by a viral mirna","volume":"317","author":"Elefant","year":"2007","journal-title":"Science"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"7457","DOI":"10.4049\/jimmunol.175.11.7457","article-title":"Human cytomegalovirus encodes an mhc class i-like molecule (ul142) that functions to inhibit nk cell lysis","volume":"175","author":"Wills","year":"2005","journal-title":"J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/ni1156","article-title":"Downregulation of natural killer cell-activating ligand cd155 by human cytomegalovirus ul141","volume":"6","author":"Tomasec","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1099\/vir.0.021931-0","article-title":"Human cytomegalovirus ul141 promotes efficient downregulation of the natural killer cell activating ligand cd112","volume":"91","author":"Sugrue","year":"2010","journal-title":"J. Gen. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Hsu, J.L., van den Boomen, D.J., Tomasec, P., Weekes, M.P., Antrobus, R., Stanton, R.J., Ruckova, E., Sugrue, D., Wilkie, G.S., and Davison, A.J. (2015). Plasma membrane profiling defines an expanded class of cell surface proteins selectively targeted for degradation by hcmv us2 in cooperation with ul141. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004811"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"11467","DOI":"10.1128\/JVI.79.17.11467-11475.2005","article-title":"Human cytomegalovirus ie1-72 activates ataxia telangiectasia mutated kinase and a p53\/p21-mediated growth arrest response","volume":"79","author":"Castillo","year":"2005","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"E, X., Pickering, M.T., Debatis, M., Castillo, J., Lagadinos, A., Wang, S., Lu, S., and Kowalik, T.F. (2011). An e2f1-mediated DNA damage response contributes to the replication of human cytomegalovirus. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001342"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.4049\/jimmunol.1502527","article-title":"Distinct roles for human cytomegalovirus immediate early proteins ie1 and ie2 in the transcriptional regulation of mica and pvr\/cd155 expression","volume":"197","author":"Pignoloni","year":"2016","journal-title":"J. Immunol."},{"key":"ref_100","unstructured":"Coffin, J.M., Hughes, S.H., and Varmus, H.E. (1997). Pathogenesis of hiv and siv. Retroviruses, Cold Spring Harbor Laboratory Press."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Zicari, S., Sessa, L., Cotugno, N., Ruggiero, A., Morrocchi, E., Concato, C., Rocca, S., Zangari, P., Manno, E.C., and Palma, P. (2019). Immune activation, inflammation, and non-aids co-morbidities in hiv-infected patients under long-term art. Viruses, 11.","DOI":"10.3390\/v11030200"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/8394","article-title":"Latent infection of cd4+ t cells provides a mechanism for lifelong persistence of hiv-1, even in patients on effective combination therapy","volume":"5","author":"Finzi","year":"1999","journal-title":"Nat. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nm.4108","article-title":"International aids society global scientific strategy: Towards an hiv cure 2016","volume":"22","author":"Deeks","year":"2016","journal-title":"Nat. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","article-title":"Targeting the latent reservoir for hiv-1","volume":"48","author":"Sengupta","year":"2018","journal-title":"Immunity"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1056\/NEJMc1315498","article-title":"Absence of hiv-1 after treatment cessation in an infant","volume":"370","author":"Persaud","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41467-019-08311-0","article-title":"A child with perinatal hiv infection and long-term sustained virological control following antiretroviral treatment cessation","volume":"10","author":"Violari","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1056\/NEJMc1413931","article-title":"Viremic relapse after hiv-1 remission in a perinatally infected child","volume":"372","author":"Luzuriaga","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Rocca, S., Zangari, P., Cotugno, N., De Rossi, A., Ferns, B., Petricone, D., Rinaldi, S., Giaquinto, C., Bernardi, S., and Rojo, P. (2018). Human immunodeficiency virus (hiv)-antibody repertoire estimates reservoir size and time of antiretroviral therapy initiation in virally suppressed perinatally hiv-infected children. J. Pediatric. Infect. Dis. Soc.","DOI":"10.1093\/jpids\/piy080"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1146\/annurev.micro.50.1.825","article-title":"Immunopathogenesis of hiv infection","volume":"50","author":"Pantaleo","year":"1996","journal-title":"Annu Rev. Microbiol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nri1711","article-title":"Nk cells in hiv infection: Paradigm for protection or targets for ambush","volume":"5","author":"Fauci","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s11904-016-0310-3","article-title":"Nk cells in hiv disease","volume":"13","author":"Scully","year":"2016","journal-title":"Curr. HIV\/AIDS Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/00042560-199511000-00005","article-title":"Natural killer cell immunodeficiency in hiv disease is manifest by profoundly decreased numbers of cd16+cd56+ cells and expansion of a population of cd16dimcd56- cells with low lytic activity","volume":"10","author":"Hu","year":"1995","journal-title":"J. Acquir. Immune Defic Syndr. Hum Retrovirol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2886","DOI":"10.1073\/pnas.0409872102","article-title":"Characterization of cd56-\/cd16+ natural killer (nk) cells: A highly dysfunctional nk subset expanded in hiv-infected viremic individuals","volume":"102","author":"Mavilio","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"15011","DOI":"10.1073\/pnas.2336091100","article-title":"Natural killer cells in hiv-1 infection: Dichotomous effects of viremia on inhibitory and activating receptors and their functional correlates","volume":"100","author":"Mavilio","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/eji.200635989","article-title":"Increased natural cytotoxicity receptor expression and relevant il-10 production in nk cells from chronically infected viremic hcv patients","volume":"37","author":"Fogli","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.virol.2010.05.014","article-title":"Mhc class i chain-related protein a shedding in chronic hiv-1 infection is associated with profound nk cell dysfunction","volume":"406","author":"Nolting","year":"2010","journal-title":"Virology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1084\/jem.20060894","article-title":"Characterization of the defective interaction between a subset of natural killer cells and dendritic cells in hiv-1 infection","volume":"203","author":"Mavilio","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1089\/vim.2006.19.576","article-title":"Expression of human cd226 on t cells and natural killer cells and of soluble cd226 in plasma of hiv-1-infected chinese patients","volume":"19","author":"Ye","year":"2006","journal-title":"Viral Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Mahapatra, S., Shearer, W.T., Minard, C.G., Mace, E., Paul, M., and Orange, J.S. (2019). Nk cells in treated hiv-infected children display altered phenotype and function. J. Allergy Clin Immunol.","DOI":"10.1016\/j.jaci.2018.11.052"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2664","DOI":"10.1099\/vir.0.055541-0","article-title":"The human immunodeficiency virus type 1 vpr protein upregulates pvr via activation of the atr-mediated DNA damage response pathway","volume":"94","author":"Vassena","year":"2013","journal-title":"J. Gen Virol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4496","DOI":"10.1128\/JVI.05788-11","article-title":"The human immunodeficiency virus type 1 nef and vpu proteins downregulate the natural killer cell-activating ligand pvr","volume":"86","author":"Matusali","year":"2012","journal-title":"J. Virol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.virol.2014.07.034","article-title":"Hiv-1 vpu mediated downregulation of cd155 requires alanine residues 10, 14 and 18 of the transmembrane domain","volume":"464\u2013465","author":"Bolduan","year":"2014","journal-title":"Virology"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAI.0000000000000917","article-title":"Cell surface downregulation of nk cell ligands by patient-derived hiv-1 vpu and nef alleles","volume":"72","author":"Galaski","year":"2016","journal-title":"J. Acquir Immune Defic Syndr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1089\/aid.2015.0375","article-title":"Cd155 on hiv-infected cells is not modulated by hiv-1 vpu and nef but synergizes with nkg2d ligands to trigger nk cell lysis of autologous primary hiv-infected cells","volume":"33","author":"Davis","year":"2017","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.imlet.2013.03.003","article-title":"Successfully treated hiv-infected patients have differential expression of nk cell receptors (nkp46 and nkp30) according to aids status at presentation","volume":"152","author":"Bisio","year":"2013","journal-title":"Immunol. Lett."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Tremblay-McLean, A., Bruneau, J., Lebouche, B., Lisovsky, I., Song, R., and Bernard, N.F. (2017). Expression profiles of ligands for activating natural killer cell receptors on hiv infected and uninfected cd4(+) t cells. Viruses, 9.","DOI":"10.3390\/v9100295"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(00)04638-9","article-title":"Herpes simplex virus infections","volume":"357","author":"Whitley","year":"2001","journal-title":"Lancet"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/infdis\/jit458","article-title":"Seroprevalence of herpes simplex virus types 1 and 2--united states, 1999-2010","volume":"209","author":"Bradley","year":"2014","journal-title":"J. Infect Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1002\/rmv.531","article-title":"Understanding hsv-1 entry glycoproteins","volume":"17","author":"Reske","year":"2007","journal-title":"Rev. Med. Virol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2903","DOI":"10.1073\/pnas.0608374104","article-title":"Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins d, h, l, and b","volume":"104","author":"Subramanian","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1080\/13550280590924214","article-title":"Nectin-1\/hvec mediates herpes simplex virus type 1 entry into primary human sensory neurons and fibroblasts","volume":"11","author":"Simpson","year":"2005","journal-title":"J. Neurovirol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"7064","DOI":"10.1128\/JVI.72.9.7064-7074.1998","article-title":"Herpes simplex virus glycoprotein d can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry","volume":"72","author":"Krummenacher","year":"1998","journal-title":"J. Virol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/1743-422X-3-105","article-title":"Nectin-2-mediated entry of a syncytial strain of herpes simplex virus via ph-independent fusion with the plasma membrane of chinese hamster ovary cells","volume":"3","author":"Delboy","year":"2006","journal-title":"Virol. J."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1126\/science.280.5369.1618","article-title":"Entry of alphaherpesviruses mediated by poliovirus receptor-related protein 1 and poliovirus receptor","volume":"280","author":"Geraghty","year":"1998","journal-title":"Science"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"16118","DOI":"10.1073\/pnas.1409485111","article-title":"Modulation of cd112 by the alphaherpesvirus gd protein suppresses dnam-1-dependent nk cell-mediated lysis of infected cells","volume":"111","author":"Grauwet","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0166-3542(99)00075-3","article-title":"The role of natural killer cells in protection of mice against death and corneal scarring following ocular hsv-1 infection","volume":"45","author":"Ghiasi","year":"2000","journal-title":"Antiviral Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/1743-422X-2-56","article-title":"Re-evaluating the role of natural killer cells in innate resistance to herpes simplex virus type 1","volume":"2","author":"Halford","year":"2005","journal-title":"Virol. J."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1046\/j.1365-2567.2001.01180.x","article-title":"Reduced herpes simplex virus type 1 latency in flt-3 ligand-treated mice is associated with enhanced numbers of natural killer and dendritic cells","volume":"102","author":"Smith","year":"2001","journal-title":"Immunology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"10168","DOI":"10.1128\/JVI.77.18.10168-10171.2003","article-title":"Interleukin-15 and natural killer and nkt cells play a critical role in innate protection against genital herpes simplex virus type 2 infection","volume":"77","author":"Ashkar","year":"2003","journal-title":"J. Virol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"10820","DOI":"10.1128\/JVI.00365-08","article-title":"Natural killer cells as novel helpers in anti-herpes simplex virus immune response","volume":"82","author":"Nandakumar","year":"2008","journal-title":"J. Virol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1128\/JVI.01907-08","article-title":"Dendritic cells are required for optimal activation of natural killer functions following primary infection with herpes simplex virus type 1","volume":"83","author":"Kassim","year":"2009","journal-title":"J. Virol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/j.1365-2567.2009.03170.x","article-title":"Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2","volume":"129","author":"Long","year":"2010","journal-title":"Immunology"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1016\/j.jaci.2016.06.034","article-title":"Defective natural killer cell activity in a mouse model of eczema herpeticum","volume":"139","author":"Kawakami","year":"2017","journal-title":"J. Allergy Clin Immunol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cellimm.2007.06.002","article-title":"Natural killer cell receptor expression in patients with severe and recurrent herpes simplex virus-1 (hsv-1) infections","volume":"246","author":"Carter","year":"2007","journal-title":"Cell Immunol."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Bjorkstrom, N.K., Svensson, A., Malmberg, K.J., Eriksson, K., and Ljunggren, H.G. (2011). Characterization of natural killer cell phenotype and function during recurrent human hsv-2 infection. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027664"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/j.1365-3083.2009.02241.x","article-title":"Herpes simplex virus infection downmodulates nkg2d ligand expression","volume":"69","author":"Schepis","year":"2009","journal-title":"Scand J. Immunol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"8985","DOI":"10.1128\/JVI.77.16.8985-8999.2003","article-title":"Cellular localization of nectin-1 and glycoprotein d during herpes simplex virus infection","volume":"77","author":"Krummenacher","year":"2003","journal-title":"J. Virol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"13678","DOI":"10.1128\/JVI.01906-14","article-title":"Crystal structure of herpes simplex virus 2 gd bound to nectin-1 reveals a conserved mode of receptor recognition","volume":"88","author":"Lu","year":"2014","journal-title":"J. Virol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.virol.2016.09.019","article-title":"Herpes simplex virus glycoprotein d relocates nectin-1 from intercellular contacts","volume":"499","author":"Bhargava","year":"2016","journal-title":"Virology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/ncomms1571","article-title":"Binding of herpes simplex virus glycoprotein d to nectin-1 exploits host cell adhesion","volume":"2","author":"Zhang","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.virol.2007.11.012","article-title":"The herpes simplex virus receptor nectin-1 is down-regulated after trans-interaction with glycoprotein d","volume":"373","author":"Stiles","year":"2008","journal-title":"Virology"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.virol.2009.12.034","article-title":"Glycoprotein d actively induces rapid internalization of two nectin-1 isoforms during herpes simplex virus entry","volume":"399","author":"Stiles","year":"2010","journal-title":"Virology"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1002\/jmv.25384","article-title":"Evaluation of the antiviral potential of the soluble forms of glycoprotein d receptors on ocular herpes caused by hsv-1 and hsv-2 infections in a transgenic mouse model","volume":"91","author":"Fujimoto","year":"2019","journal-title":"J. Med. Virol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"21348","DOI":"10.18632\/oncotarget.25096","article-title":"Comparison of infectivity and spread between hsv-1 and hsv-2 based oncolytic viruses on tumor cells with different receptor expression profiles","volume":"9","author":"Fu","year":"2018","journal-title":"Oncotarget"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"5265","DOI":"10.1158\/1078-0432.CCR-16-1003","article-title":"Bortezomib treatment sensitizes oncolytic hsv-1-treated tumors to nk cell immunotherapy","volume":"22","author":"Yoo","year":"2016","journal-title":"Clin Cancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.msard.2017.06.002","article-title":"Ebv and ms: Major cause, minor contribution or red-herring?","volume":"16","author":"Burnard","year":"2017","journal-title":"Mult. Scler. Relat. Disord"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1073\/pnas.2237267100","article-title":"Demonstration of the burkitt\u2019s lymphoma epstein-barr virus phenotype in dividing latently infected memory cells in vivo","volume":"101","author":"Hochberg","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_158","first-page":"581","article-title":"Epstein-barr virus and nasopharyngeal carcinoma","volume":"33","author":"Young","year":"2014","journal-title":"Chin J. Cancer"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.3389\/fimmu.2018.01103","article-title":"Inherited immunodeficiencies with high predisposition to epstein-barr virus-driven lymphoproliferative diseases","volume":"9","author":"Latour","year":"2018","journal-title":"Front Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1128\/JVI.79.2.1296-1307.2005","article-title":"Terminal differentiation into plasma cells initiates the replicative cycle of epstein-barr virus in vivo","volume":"79","author":"Laichalk","year":"2005","journal-title":"J. Virol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fimmu.2016.00323","article-title":"Nk cell influence on the outcome of primary epstein-barr virus infection","volume":"7","author":"Chijioke","year":"2016","journal-title":"Front Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1111\/j.1365-2141.2005.05452.x","article-title":"The immune response to primary ebv infection: A role for natural killer cells","volume":"129","author":"Williams","year":"2005","journal-title":"Br. J. Haematol."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Dunmire, S.K., Grimm, J.M., Schmeling, D.O., Balfour, H.H., and Hogquist, K.A. (2015). The incubation period of primary epstein-barr virus infection: Viral dynamics and immunologic events. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005286"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2533","DOI":"10.1182\/blood-2014-01-553024","article-title":"Role for early-differentiated natural killer cells in infectious mononucleosis","volume":"124","author":"Azzi","year":"2014","journal-title":"Blood"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1128\/JVI.01777-06","article-title":"The switch from latent to productive infection in epstein-barr virus-infected b cells is associated with sensitization to nk cell killing","volume":"81","author":"Pappworth","year":"2007","journal-title":"J. Virol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1128\/JVI.01932-15","article-title":"Induction of the lytic cycle sensitizes epstein-barr virus-infected b cells to nk cell killing that is counteracted by virus-mediated nk cell evasion mechanisms in the late lytic cycle","volume":"90","author":"Williams","year":"2016","journal-title":"J. Virol."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Pende, D., Meazza, R., Marcenaro, S., Arico, M., and Bottino, C. (2018). 2b4 dysfunction in xlp1 nk cells: More than inability to control ebv infection. Clin Immunol.","DOI":"10.1016\/j.clim.2018.10.022"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"e00305","DOI":"10.1128\/mSphere.00305-17","article-title":"Epstein-barr virus induces adhesion receptor cd226 (dnam-1) expression during primary b-cell transformation into lymphoblastoid cell lines","volume":"2","author":"Grossman","year":"2017","journal-title":"mSphere"},{"key":"ref_169","doi-asserted-by":"crossref","unstructured":"Chigbu, D.I., Loonawat, R., Sehgal, M., Patel, D., and Jain, P. (2019). Hepatitis c virus infection: Host(-)virus interaction and mechanisms of viral persistence. Cells, 8.","DOI":"10.3390\/cells8040376"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1053\/j.gastro.2010.12.032","article-title":"Increasing prevalence of hcc and cirrhosis in patients with chronic hepatitis c virus infection","volume":"140","author":"Kanwal","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1136\/gut.2005.076463","article-title":"Surface expression and cytolytic function of natural killer cell receptors is altered in chronic hepatitis c","volume":"55","author":"Nattermann","year":"2006","journal-title":"Gut"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1053\/j.gastro.2009.05.047","article-title":"Natural killer cell functional dichotomy in chronic hepatitis b and chronic hepatitis c virus infections","volume":"137","author":"Oliviero","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1053\/j.gastro.2009.08.066","article-title":"Natural killer cells are polarized toward cytotoxicity in chronic hepatitis c in an interferon-alfa-dependent manner","volume":"138","author":"Ahlenstiel","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1136\/gut.2007.130963","article-title":"Altered natural killer cell subset distributions in resolved and persistent hepatitis c virus infection following single source exposure","volume":"57","author":"McGrath","year":"2008","journal-title":"Gut"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1111\/j.1365-2893.2008.01014.x","article-title":"Natural killer cells suppress full cycle hcv infection of human hepatocytes","volume":"15","author":"Wang","year":"2008","journal-title":"J. Viral Hepat."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1126\/science.1097670","article-title":"Hla and nk cell inhibitory receptor genes in resolving hepatitis c virus infection","volume":"305","author":"Khakoo","year":"2004","journal-title":"Science"},{"key":"ref_177","first-page":"1017","article-title":"Distinct kir\/hla compound genotypes affect the kinetics of human antiviral natural killer cell responses","volume":"118","author":"Ahlenstiel","year":"2008","journal-title":"J. Clin Invest."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"5465","DOI":"10.1158\/1078-0432.CCR-13-0986","article-title":"Hla and killer immunoglobulin-like receptor genes as outcome predictors of hepatitis c virus-related hepatocellular carcinoma","volume":"19","author":"Cariani","year":"2013","journal-title":"Clin Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1002\/hep.23896","article-title":"Increased natural killer cell cytotoxicity and nkp30 expression protects against hepatitis c virus infection in high-risk individuals and inhibits replication in vitro","volume":"52","author":"Cox","year":"2010","journal-title":"Hepatology"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1053\/j.gastro.2010.01.051","article-title":"Interferon-alpha-induced trail on natural killer cells is associated with control of hepatitis c virus infection","volume":"138","author":"Stegmann","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1136\/gut.2010.212555","article-title":"Natural killer cells and hepatitis c: Action and reaction","volume":"60","author":"Cheent","year":"2011","journal-title":"Gut"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"12557","DOI":"10.1128\/JVI.00838-11","article-title":"Cell-to-cell contact with hepatitis c virus-infected cells reduces functional capacity of natural killer cells","volume":"85","author":"Yoon","year":"2011","journal-title":"J. Virol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1084\/jem.20011124","article-title":"Inhibition of natural killer cells through engagement of cd81 by the major hepatitis c virus envelope protein","volume":"195","author":"Crotta","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1084\/jem.20011145","article-title":"Binding of the hepatitis c virus envelope protein e2 to cd81 inhibits natural killer cell functions","volume":"195","author":"Tseng","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/cmi.2008.60","article-title":"Hepatitis c virus infection downregulates the ligands of the activating receptor nkg2d","volume":"5","author":"Wen","year":"2008","journal-title":"Cell Mol. Immunol."},{"key":"ref_186","doi-asserted-by":"crossref","unstructured":"Sene, D., Levasseur, F., Abel, M., Lambert, M., Camous, X., Hernandez, C., Pene, V., Rosenberg, A.R., Jouvin-Marche, E., and Marche, P.N. (2010). Hepatitis c virus (hcv) evades nkg2d-dependent nk cell responses through ns5a-mediated imbalance of inflammatory cytokines. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001184"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/s41467-019-09212-y","article-title":"Nkg2a is a nk cell exhaustion checkpoint for hcv persistence","volume":"10","author":"Zhang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1002\/eji.201041361","article-title":"Activating nk cell receptor expression\/function (nkp30, nkp46, dnam-1) during chronic viraemic hcv infection is associated with the outcome of combined treatment","volume":"41","author":"Bozzano","year":"2011","journal-title":"Eur. J. Immunol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1093\/infdis\/jis210","article-title":"Interferon alpha-stimulated natural killer cells from patients with acute hepatitis c virus (hcv) infection recognize hcv-infected and uninfected hepatoma cells via dnax accessory molecule-1","volume":"205","author":"Stegmann","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"33","DOI":"10.4103\/0974-777X.52979","article-title":"Association between hepatitis c and hepatocellular carcinoma","volume":"1","author":"Melo","year":"2009","journal-title":"J. Glob. Infect Dis."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/s41590-018-0163-6","article-title":"Natural killer cell specificity for viral infections","volume":"19","author":"Hammer","year":"2018","journal-title":"Nat. Immunol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1159\/000324176","article-title":"Natural killer cell responses to viral infection","volume":"3","author":"Brandstadter","year":"2011","journal-title":"J. Innate Immun."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.coviro.2013.05.011","article-title":"Evasion of adaptive and innate immune response mechanisms by gamma-herpesviruses","volume":"3","author":"Feng","year":"2013","journal-title":"Curr. Opin. Virol."},{"key":"ref_194","doi-asserted-by":"crossref","unstructured":"Iguchi-Manaka, A., Okumura, G., Kojima, H., Cho, Y., Hirochika, R., Bando, H., Sato, T., Yoshikawa, H., Hara, H., and Shibuya, A. (2016). Increased soluble cd155 in the serum of cancer patients. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152982"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1172\/JCI123375","article-title":"Cytomegalovirus promotes murine glioblastoma growth via pericyte recruitment and angiogenesis","volume":"130","author":"Krenzlin","year":"2019","journal-title":"J. Clin Invest."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1182\/blood-2005-04-1351","article-title":"Synergy among receptors on resting nk cells for the activation of natural cytotoxicity and cytokine secretion","volume":"107","author":"Bryceson","year":"2006","journal-title":"Blood"},{"key":"ref_197","first-page":"66","article-title":"Human nk cell diversity in viral infection: Ramifications of ramification","volume":"7","author":"Blish","year":"2016","journal-title":"Front Immunol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.3389\/fimmu.2018.01452","article-title":"Diverse impacts of hiv latency-reversing agents on cd8+ t-cell function: Implications for hiv cure","volume":"9","author":"Clutton","year":"2018","journal-title":"Front Immunol."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Ke, R., Conway, J.M., Margolis, D.M., and Perelson, A.S. (2018). Determinants of the efficacy of hiv latency-reversing agents and implications for drug and treatment design. JCI Insight, 3.","DOI":"10.1172\/jci.insight.123052"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3389\/fimmu.2016.00356","article-title":"Hiv latency-reversing agents have diverse effects on natural killer cell function","volume":"7","author":"Garrido","year":"2016","journal-title":"Front Immunol."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fimmu.2018.01514","article-title":"In vitro exposure to prostratin but not bryostatin-1 improves natural killer cell functions including killing of cd4(+) t cells harboring reactivated human immunodeficiency virus","volume":"9","author":"Desimio","year":"2018","journal-title":"Front Immunol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1038\/s41598-019-40760-x","article-title":"Hexamethylene bisacetamide impairs nk cell-mediated clearance of acute t lymphoblastic leukemia cells and hiv-1-infected t cells that exit viral latency","volume":"9","author":"Giuliani","year":"2019","journal-title":"Sci Rep"},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.molmed.2017.10.002","article-title":"Boosting natural killer cell-based immunotherapy with anticancer drugs: A perspective","volume":"23","author":"Cifaldi","year":"2017","journal-title":"Trends Mol. Med."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/1389450119666180426103558","article-title":"DNA related enzymes as molecular targets for antiviral and antitumoral chemotherapy. A natural overview of the current perspectives","volume":"20","author":"Garro","year":"2019","journal-title":"Curr. Drug Targets"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/ni.3518","article-title":"Targeting natural killer cells in cancer immunotherapy","volume":"17","author":"Guillerey","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"20891","DOI":"10.18632\/oncotarget.25058","article-title":"Natural killer cells as a therapeutic tool for infectious diseases - current status and future perspectives","volume":"9","author":"Schmidt","year":"2018","journal-title":"Oncotarget"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1038\/mt.2015.102","article-title":"Hiv-specific immunity derived from chimeric antigen receptor-engineered stem cells","volume":"23","author":"Zhen","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"14812","DOI":"10.1002\/jcp.28280","article-title":"Memory and car-nk cell-based novel approaches for hiv vaccination and eradication","volume":"234","author":"Mazarzaei","year":"2019","journal-title":"J. Cell Physiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3715\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:11:03Z","timestamp":1760188263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3715"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,30]]},"references-count":208,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20153715"],"URL":"https:\/\/doi.org\/10.3390\/ijms20153715","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,30]]}}}