{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:04:45Z","timestamp":1790373885514,"version":"4.1.0"},"reference-count":133,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,7]],"date-time":"2019-09-07T00:00:00Z","timestamp":1567814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union's Framework Program for Research and Innovation Horizon 2020 (2014-2020)","award":["703896"],"award-info":[{"award-number":["703896"]}]},{"name":"IZKF Erlangen","award":["J57"],"award-info":[{"award-number":["J57"]}]},{"name":"IZKF Erlangen","award":["A66"],"award-info":[{"award-number":["A66"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Herpesviruses are important pathogens that can cause significant morbidity and mortality in the human population. Herpesviruses have a double-stranded DNA genome, and viral genome replication takes place inside the nucleus. Upon entering the nucleus, herpesviruses have to overcome the obstacle of cellular proteins in order to enable viral gene expression and genome replication. In this review, we want to highlight cellular proteins that sense incoming viral genomes of the DNA-damage repair (DDR) pathway and of PML-nuclear bodies (PML-NBs) that all can act as antiviral restriction factors within the first hours after the viral genome is released into the nucleus. We show the function and significance of both nuclear DNA sensors, the DDR and PML-NBs, and demonstrate for three human herpesviruses of the alpha-, beta- and gamma-subfamilies, HSV-1, HCMV and KSHV respectively, how viral tegument proteins antagonize these pathways.<\/jats:p>","DOI":"10.3390\/jcm8091408","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T04:12:40Z","timestamp":1568002360000},"page":"1408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Early Nuclear Events after Herpesviral Infection"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1900-5891","authenticated-orcid":false,"given":"Florian","family":"Full","sequence":"first","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-3863","authenticated-orcid":false,"given":"Armin","family":"Ensser","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Molecular Virology, University Hospital Erlangen, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,7]]},"reference":[{"key":"ref_1","unstructured":"Pellet, P.E., and Roizman, B. (2013). Fields Virology, Wolters Kluwer."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Looker, K.J., Magaret, A.S., May, M.T., Turner, K.M., Vickerman, P., Gottlieb, S.L., and Newman, L.M. (2015). Global and Regional Estimates of Prevalent and Incident Herpes Simplex Virus Type 1 Infections in 2012. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140765"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Emery, V.C., and Clark, D.A. (2007). HHV-6A, 6B, and 7: Persistence in the population, epidemiology and transmission. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, Cambridge University Press.","DOI":"10.1017\/CBO9780511545313.050"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hjalgrim, H., Friborg, J., and Melbye, M. (2007). The epidemiology of EBV and its association with malignant disease. Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis, Cambridge University Press.","DOI":"10.1017\/CBO9780511545313.054"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1038\/s41586-019-1248-6","article-title":"Cryo-EM structures of herpes simplex virus type 1 portal vertex and packaged genome","volume":"570","author":"Liu","year":"2019","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature07725","article-title":"AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC","volume":"458","author":"Hornung","year":"2009","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1126\/science.1232458","article-title":"Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway","volume":"339","author":"Sun","year":"2013","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1126\/science.1229963","article-title":"Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA","volume":"339","author":"Wu","year":"2013","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.virol.2015.02.009","article-title":"Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity","volume":"479","author":"Knipe","year":"2015","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"526","DOI":"10.4161\/nucl.21979","article-title":"Virus strategies for passing the nuclear envelope barrier","volume":"3","author":"Kobiler","year":"2012","journal-title":"Nucleus"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E4492","DOI":"10.1073\/pnas.1316194110","article-title":"Nuclear interferon-inducible protein 16 promotes silencing of herpesviral and transfected DNA","volume":"110","author":"Orzalli","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E3008","DOI":"10.1073\/pnas.1211302109","article-title":"Nuclear IFI16 induction of IRF-3 signaling during herpesviral infection and degradation of IFI16 by the viral ICP0 protein","volume":"109","author":"Orzalli","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10558","DOI":"10.1073\/pnas.1203447109","article-title":"Acetylation modulates cellular distribution and DNA sensing ability of interferon-inducible protein IFI16","volume":"109","author":"Li","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Komatsu, T., Nagata, K., and Wodrich, H. (2016). The Role of Nuclear Antiviral Factors against Invading DNA Viruses: The Immediate Fate of Incoming Viral Genomes. Viruses, 8.","DOI":"10.3390\/v8100290"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/ni.1932","article-title":"IFI16 is an innate immune sensor for intracellular DNA","volume":"11","author":"Unterholzner","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ansari, M.A., Dutta, S., Veettil, M.V., Dutta, D., Iqbal, J., Kumar, B., Roy, A., Chikoti, L., Singh, V.V., and Chandran, B. (2015). Herpesvirus Genome Recognition Induced Acetylation of Nuclear IFI16 Is Essential for Its Cytoplasmic Translocation, Inflammasome and IFN-beta Responses. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005019"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E1773","DOI":"10.1073\/pnas.1424637112","article-title":"cGAS-mediated stabilization of IFI16 promotes innate signaling during herpes simplex virus infection","volume":"112","author":"Orzalli","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1128\/JVI.02249-15","article-title":"Dynamic Response of IFI16 and Promyelocytic Leukemia Nuclear Body Components to Herpes Simplex Virus 1 Infection","volume":"90","author":"Everett","year":"2016","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lum, K.K., Howard, T.R., Pan, C., and Cristea, I.M. (2019). Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA. MBio.","DOI":"10.1128\/mBio.01428-19"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Merkl, P.E., and Knipe, D.M. (2019). Role for a Filamentous Nuclear Assembly of IFI16, DNA, and Host Factors in Restriction of Herpesviral Infection. MBio.","DOI":"10.1128\/mBio.02621-18"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gariano, G.R., Dell\u2019Oste, V., Bronzini, M., Gatti, D., Luganini, A., De Andrea, M., Gribaudo, G., Gariglio, M., and Landolfo, S. (2012). The intracellular DNA sensor IFI16 gene acts as restriction factor for human cytomegalovirus replication. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002498"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.chom.2013.10.007","article-title":"Human cytomegalovirus tegument protein pUL83 inhibits IFI16-mediated DNA sensing for immune evasion","volume":"14","author":"Li","year":"2013","journal-title":"Cell Host Microbe."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"13422","DOI":"10.1128\/JVI.02474-13","article-title":"The viral ubiquitin ligase ICP0 is neither sufficient nor necessary for degradation of the cellular DNA sensor IFI16 during herpes simplex virus 1 infection","volume":"87","author":"Anderson","year":"2013","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1074\/mcp.M114.047068","article-title":"Interactions of the Antiviral Factor Interferon Gamma-Inducible Protein 16 (IFI16) Mediate Immune Signaling and Herpes Simplex Virus-1 Immunosuppression","volume":"14","author":"Diner","year":"2015","journal-title":"Mol. Cell Proteomics."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8351","DOI":"10.1128\/JVI.00939-16","article-title":"Relative Contributions of Herpes Simplex Virus 1 ICP0 and vhs to Loss of Cellular IFI16 Vary in Different Human Cell Types","volume":"90","author":"Orzalli","year":"2016","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8822","DOI":"10.1128\/JVI.01003-16","article-title":"Nuclear Innate Immune DNA Sensor IFI16 Is Degraded during Lytic Reactivation of Kaposi\u2019s Sarcoma-Associated Herpesvirus (KSHV): Role of IFI16 in Maintenance of KSHV Latency","volume":"90","author":"Roy","year":"2016","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.chom.2011.04.008","article-title":"IFI16 acts as a nuclear pathogen sensor to induce the inflammasome in response to Kaposi Sarcoma-associated herpesvirus infection","volume":"9","author":"Kerur","year":"2011","journal-title":"Cell Host Microbe."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Dutta, D., Dutta, S., Veettil, M.V., Roy, A., Ansari, M.A., Iqbal, J., Chikoti, L., Kumar, B., Johnson, K.E., and Chandran, B. (2015). BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-beta Responses. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1005030"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Iqbal, J., Ansari, M.A., Kumar, B., Dutta, D., Roy, A., Chikoti, L., Pisano, G., Dutta, S., Vahedi, S., and Veettil, M.V. (2016). Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-beta Responses. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005967"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Johnson, K.E., Bottero, V., Flaherty, S., Dutta, S., Singh, V.V., and Chandran, B. (2014). IFI16 restricts HSV-1 replication by accumulating on the hsv-1 genome, repressing HSV-1 gene expression, and directly or indirectly modulating histone modifications. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004503"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Alandijany, T., Roberts, A.P.E., Conn, K.L., Loney, C., McFarlane, S., Orr, A., and Boutell, C. (2018). Distinct temporal roles for the promyelocytic leukaemia (PML) protein in the sequential regulation of intracellular host immunity to HSV-1 infection. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1006927"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1128\/JVI.02545-15","article-title":"An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies","volume":"90","author":"Komatsu","year":"2016","journal-title":"J. Virol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.bbrc.2016.03.078","article-title":"Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes","volume":"473","author":"Komatsu","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Cabral, J.M., Oh, H.S., and Knipe, D.M. (2018). ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress. Elife.","DOI":"10.7554\/eLife.40228.029"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1146\/annurev-micro-091313-103409","article-title":"Cellular sensing of viral DNA and viral evasion mechanisms","volume":"68","author":"Orzalli","year":"2014","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Stempel, M., Chan, B., and Brinkmann, M.M. (2019). Coevolution pays off: Herpesviruses have the license to escape the DNA sensing pathway. Med. Microbiol. Immunol.","DOI":"10.1007\/s00430-019-00582-0"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1146\/annurev-virology-092917-043534","article-title":"Virus DNA Replication and the Host DNA Damage Response","volume":"5","author":"Weitzman","year":"2018","journal-title":"Annu. Rev. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.cell.2015.07.058","article-title":"Viral and Cellular Genomes Activate Distinct DNA Damage Responses","volume":"162","author":"Shah","year":"2015","journal-title":"Cell"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/nature00863","article-title":"Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex","volume":"418","author":"Stracker","year":"2002","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7034","DOI":"10.1128\/JVI.00029-07","article-title":"Adenovirus E4 34k and E1b 55k oncoproteins target host DNA ligase IV for proteasomal degradation","volume":"81","author":"Baker","year":"2007","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Schrank, B., and Gautier, J. (2019). Assembling nuclear domains: Lessons from DNA repair. J. Cell Biol.","DOI":"10.1083\/jcb.201904202"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10146","DOI":"10.1128\/JVI.01723-14","article-title":"Structure of the herpes simplex virus 1 genome: Manipulation of nicks and gaps can abrogate infectivity and alter the cellular DNA damage response","volume":"88","author":"Smith","year":"2014","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1126\/science.aab3389","article-title":"Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection","volume":"350","author":"Blackburn","year":"2015","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-981-10-7230-7_10","article-title":"Chromosomal Integration by Human Herpesviruses 6A and 6B","volume":"1045","author":"Flamand","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1002\/jmv.21299","article-title":"Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal sites","volume":"80","author":"Nacheva","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1073\/pnas.0913586107","article-title":"The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in vitro","volume":"107","author":"Arbuckle","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1128\/JVI.02504-12","article-title":"Efficient herpes simplex virus 1 replication requires cellular ATR pathway proteins","volume":"87","author":"Mohni","year":"2013","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"12152","DOI":"10.1128\/JVI.01643-10","article-title":"ATR and ATRIP are recruited to herpes simplex virus type 1 replication compartments even though ATR signaling is disabled","volume":"84","author":"Mohni","year":"2010","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Edwards, T.G., Bloom, D.C., and Fisher, C. (2018). The ATM and Rad3-Related (ATR) Protein Kinase Pathway Is Activated by Herpes Simplex Virus 1 and Required for Efficient Viral Replication. J. Virol.","DOI":"10.1128\/JVI.01884-17"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1128\/JVI.01913-14","article-title":"The putative herpes simplex virus 1 chaperone protein UL32 modulates disulfide bond formation during infection","volume":"89","author":"Albright","year":"2015","journal-title":"J. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Mohni, K.N., Smith, S., Dee, A.R., Schumacher, A.J., and Weller, S.K. (2013). Herpes simplex virus type 1 single strand DNA binding protein and helicase\/primase complex disable cellular ATR signaling. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003652"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1242\/jcs.02981","article-title":"Herpes simplex virus type I disrupts the ATR-dependent DNA-damage response during lytic infection","volume":"119","author":"Wilkinson","year":"2006","journal-title":"J. Cell Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5844","DOI":"10.1073\/pnas.0501916102","article-title":"DNA repair proteins affect the lifecycle of herpes simplex virus 1","volume":"102","author":"Lilley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.tim.2007.01.003","article-title":"Using or abusing: Viruses and the cellular DNA damage response","volume":"15","author":"Lilley","year":"2007","journal-title":"Trends. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Dembowski, J.A., Dremel, S.E., and DeLuca, N.A. (2017). Replication-Coupled Recruitment of Viral and Cellular Factors to Herpes Simplex Virus Type 1 Replication Forks for the Maintenance and Expression of Viral Genomes. PLoS Pathog., 13.","DOI":"10.1371\/journal.ppat.1006166"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Hollingworth, R., Horniblow, R.D., Forrest, C., Stewart, G.S., and Grand, R.J. (2017). Localization of Double-Strand Break Repair Proteins to Viral Replication Compartments following Lytic Reactivation of Kaposi\u2019s Sarcoma-Associated Herpesvirus. J. Virol.","DOI":"10.1128\/JVI.00930-17"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.3390\/v7062752","article-title":"Activation of DNA Damage Response Pathways during Lytic Replication of KSHV","volume":"7","author":"Hollingworth","year":"2015","journal-title":"Viruses"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"O\u2019Dowd, J.M., Zavala, A.G., Brown, C.J., Mori, T., and Fortunato, E.A. (2012). HCMV-infected cells maintain efficient nucleotide excision repair of the viral genome while abrogating repair of the host genome. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003038"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1128\/JVI.01670-06","article-title":"Human cytomegalovirus disrupts both ataxia telangiectasia mutated protein (ATM)- and ATM-Rad3-related kinase-mediated DNA damage responses during lytic infection","volume":"81","author":"Luo","year":"2007","journal-title":"J. Virol."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","unstructured":"Xiaofei, E., 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_62","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1128\/JVI.03423-13","article-title":"A novel DDB2-ATM feedback loop regulates human cytomegalovirus replication","volume":"88","author":"Xiaofei","year":"2014","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2155","DOI":"10.3390\/v6052155","article-title":"The DNA damage response induced by infection with human cytomegalovirus and other viruses","volume":"6","author":"Xiaofei","year":"2014","journal-title":"Viruses"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s00430-015-0396-z","article-title":"Human cytomegalovirus riding the cell cycle","volume":"204","author":"Spector","year":"2015","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Trigg, B.J., Lauer, K.B., Fernandes Dos Santos, P., Coleman, H., Balmus, G., Mansur, D.S., and Ferguson, B.J. (2017). The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection. Viruses, 9.","DOI":"10.3390\/v9110342"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Reichel, A., Stilp, A.C., Scherer, M., Reuter, N., Lukassen, S., Kasmapour, B., Schreiner, S., Cicin-Sain, L., Winterpacht, A., and Stamminger, T. (2018). Chromatin-Remodeling Factor SPOC1 Acts as a Cellular Restriction Factor against Human Cytomegalovirus by Repressing the Major Immediate Early Promoter. J. Virol.","DOI":"10.1128\/JVI.00342-18"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Schreiner, S., Kinkley, S., Burck, C., Mund, A., Wimmer, P., Schubert, T., Groitl, P., Will, H., and Dobner, T. (2013). SPOC1-mediated antiviral host cell response is antagonized early in human adenovirus type 5 infection. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003775"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11363","DOI":"10.1093\/nar\/gks868","article-title":"SPOC1 modulates DNA repair by regulating key determinants of chromatin compaction and DNA damage response","volume":"40","author":"Mund","year":"2012","journal-title":"Nucleic. Acids. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7871","DOI":"10.1073\/pnas.1230643100","article-title":"Relationship of herpes simplex virus genome configuration to productive and persistent infections","volume":"100","author":"Jackson","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"12487","DOI":"10.1128\/JVI.79.19.12487-12494.2005","article-title":"Circularization of the herpes simplex virus type 1 genome upon lytic infection","volume":"79","author":"Strang","year":"2005","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"10665","DOI":"10.1073\/pnas.91.22.10665","article-title":"Rolling circle DNA replication in vitro by a complex of herpes simplex virus type 1-encoded enzymes","volume":"91","author":"Skaliter","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1128\/jvi.70.2.1132-1136.1996","article-title":"Rolling circle DNA replication by extracts of herpes simplex virus type 1-infected human cells","volume":"70","author":"Skaliter","year":"1996","journal-title":"J. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1006\/viro.1994.1375","article-title":"Identification of novel herpes simplex virus replicative intermediates by field inversion gel electrophoresis: Implications for viral DNA amplification strategies","volume":"202","author":"Zhang","year":"1994","journal-title":"Virology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1006\/viro.1994.1206","article-title":"Study of the structure of replicative intermediates of HSV-1 DNA by pulsed-field gel electrophoresis","volume":"200","author":"Severini","year":"1994","journal-title":"Virology"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3169","DOI":"10.1128\/jvi.70.5.3169-3175.1996","article-title":"Branched structures in the intracellular DNA of herpes simplex virus type 1","volume":"70","author":"Severini","year":"1996","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/15216540310001612237","article-title":"The role of DNA recombination in herpes simplex virus DNA replication","volume":"55","author":"Wilkinson","year":"2003","journal-title":"IUBMB Life"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dembowski, J.A., and DeLuca, N.A. (2018). Temporal Viral Genome-Protein Interactions Define Distinct Stages of Productive Herpesviral Infection. MBio.","DOI":"10.1101\/331272"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Ligasova, A., Liboska, R., Friedecky, D., Micova, K., Adam, T., Ozdian, T., Rosenberg, I., and Koberna, K. (2016). Dr Jekyll and Mr Hyde: A strange case of 5-ethynyl-2\u2019-deoxyuridine and 5-ethynyl-2\u2019-deoxycytidine. Open Biol.","DOI":"10.1098\/rsob.150172"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10577-013-9340-5","article-title":"EdU induces DNA damage response and cell death in mESC in culture","volume":"21","author":"Kohlmeier","year":"2013","journal-title":"Chromosome. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1128\/JVI.73.1.650-657.1999","article-title":"Herpes simplex virus type 1 immediate-early protein vmw110 induces the proteasome-dependent degradation of the catalytic subunit of DNA-dependent protein kinase","volume":"73","author":"Parkinson","year":"1999","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7471","DOI":"10.1128\/jvi.70.11.7471-7477.1996","article-title":"Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0","volume":"70","author":"Long","year":"1996","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1128\/JVI.78.11.5856-5866.2004","article-title":"Proteomics of herpes simplex virus replication compartments: Association of cellular DNA replication, repair, recombination, and chromatin remodeling proteins with ICP8","volume":"78","author":"Taylor","year":"2004","journal-title":"J. Virol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Lilley, C.E., Chaurushiya, M.S., Boutell, C., Everett, R.D., and Weitzman, M.D. (2011). The intrinsic antiviral defense to incoming HSV-1 genomes includes specific DNA repair proteins and is counteracted by the viral protein ICP0. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002084"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/emboj.2009.400","article-title":"A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses","volume":"29","author":"Lilley","year":"2010","journal-title":"EMBO J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.cell.2012.08.005","article-title":"RNF168 ubiquitinates K13-15 on H2A\/H2AX to drive DNA damage signaling","volume":"150","author":"Mattiroli","year":"2012","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Lallemand-Breitenbach, V., and de Th\u00e9, H. (2010). PML nuclear bodies. Cold Spring Harb. Perspect. Biol.","DOI":"10.1101\/cshperspect.a000661"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ceb.2018.03.011","article-title":"PML nuclear bodies: From architecture to function","volume":"52","year":"2018","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1016\/j.bbamcr.2008.08.004","article-title":"New insights into the role of the subnuclear structure ND10 for viral infection","volume":"1783","author":"Tavalai","year":"2008","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Full, F., Hahn, A.S., Grosskopf, A.K., and Ensser, A. (2017). Gammaherpesviral Tegument Proteins, PML-Nuclear Bodies and the Ubiquitin-Proteasome System. Viruses, 9.","DOI":"10.3390\/v9100308"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/978-3-319-53168-7_4","article-title":"The Human CMV IE1 Protein: An Offender of PML Nuclear Bodies","volume":"223","author":"Scherer","year":"2017","journal-title":"Adv. Anat. Embryol. Cell Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1093\/nar\/gkt064","article-title":"Control of human adenovirus type 5 gene expression by cellular Daxx\/ATRX chromatin-associated complexes","volume":"41","author":"Schreiner","year":"2013","journal-title":"Nucleic. Acids. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"10309","DOI":"10.1128\/JVI.01220-16","article-title":"Canonical and Variant Forms of Histone H3 Are Deposited onto the Human Cytomegalovirus Genome during Lytic and Latent Infections","volume":"90","author":"Albright","year":"2016","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"14350","DOI":"10.1128\/JVI.01895-14","article-title":"Viral reprogramming of the Daxx histone H3.3 chaperone during early Epstein-Barr virus infection","volume":"88","author":"Tsai","year":"2014","journal-title":"J. Virol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"McFarlane, S., Orr, A., Roberts, A.P.E., Conn, K.L., Iliev, V., Loney, C., da Silva Filipe, A., Smollett, K., Gu, Q., and Robertson, N. (2019). The histone chaperone HIRA promotes the induction of host innate immune defences in response to HSV-1 infection. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007667"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11673","DOI":"10.1093\/nar\/gkx771","article-title":"Histone chaperone HIRA deposits histone H3.3 onto foreign viral DNA and contributes to anti-viral intrinsic immunity","volume":"45","author":"Rai","year":"2017","journal-title":"Nucleic. Acids. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e02007","DOI":"10.1128\/mBio.02007-15","article-title":"Herpesviral ICP0 Protein Promotes Two Waves of Heterochromatin Removal on an Early Viral Promoter during Lytic Infection","volume":"7","author":"Lee","year":"2016","journal-title":"MBio"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1083\/jcb.138.1.5","article-title":"Human cytomegalovirus immediate early interaction with host nuclear structures: Definition of an immediate transcript environment","volume":"138","author":"Ishov","year":"1997","journal-title":"J. Cell Biol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11167","DOI":"10.1128\/JVI.01218-08","article-title":"Temporal dynamics of cytomegalovirus chromatin assembly in productively infected human cells","volume":"82","author":"Nitzsche","year":"2008","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"37652","DOI":"10.1074\/jbc.M604273200","article-title":"Human Daxx-mediated repression of human cytomegalovirus gene expression correlates with a repressive chromatin structure around the major immediate early promoter","volume":"281","author":"Woodhall","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1006\/viro.1996.0094","article-title":"Nuclear domain 10 as preexisting potential replication start sites of herpes simplex virus type-1","volume":"217","author":"Maul","year":"1996","journal-title":"Virology"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"5850","DOI":"10.1128\/JVI.01979-15","article-title":"Emerging Role of PML Nuclear Bodies in Innate Immune Signaling","volume":"90","author":"Scherer","year":"2016","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12030","DOI":"10.1128\/JVI.01575-08","article-title":"Herpes simplex virus ICP0 promotes both histone removal and acetylation on viral DNA during lytic infection","volume":"82","author":"Cliffe","year":"2008","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9689","DOI":"10.1128\/JVI.78.18.9689-9696.2004","article-title":"VP16-dependent association of chromatin-modifying coactivators and underrepresentation of histones at immediate-early gene promoters during herpes simplex virus infection","volume":"78","author":"Herrera","year":"2004","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1099\/0022-1317-75-6-1223","article-title":"The nuclear location of PML, a cellular member of the C3HC4 zinc-binding domain protein family, is rearranged during herpes simplex virus infection by the C3HC4 viral protein ICP0","volume":"75","author":"Maul","year":"1994","journal-title":"J. Gen. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1128\/JVI.72.8.6581-6591.1998","article-title":"The disruption of ND10 during herpes simplex virus infection correlates with the Vmw110- and proteasome-dependent loss of several PML isoforms","volume":"72","author":"Everett","year":"1998","journal-title":"J. Virol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1128\/JVI.02950-12","article-title":"Components of promyelocytic leukemia nuclear bodies (ND10) act cooperatively to repress herpesvirus infection","volume":"87","author":"Glass","year":"2013","journal-title":"J. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7995","DOI":"10.1128\/JVI.00734-06","article-title":"PML contributes to a cellular mechanism of repression of herpes simplex virus type 1 infection that is inactivated by ICP0","volume":"80","author":"Everett","year":"2006","journal-title":"J. Virol."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Boutell, C., Cuchet-Lourenco, D., Vanni, E., Orr, A., Glass, M., McFarlane, S., and Everett, R.D. (2011). A viral ubiquitin ligase has substrate preferential SUMO targeted ubiquitin ligase activity that counteracts intrinsic antiviral defence. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002245"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5769","DOI":"10.1128\/JVI.76.11.5769-5783.2002","article-title":"Functional interaction between the pp71 protein of human cytomegalovirus and the PML-interacting protein human Daxx","volume":"76","author":"Hofmann","year":"2002","journal-title":"J. Virol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"7705","DOI":"10.1128\/JVI.76.15.7705-7712.2002","article-title":"Daxx-mediated accumulation of human cytomegalovirus tegument protein pp71 at ND10 facilitates initiation of viral infection at these nuclear domains","volume":"76","author":"Ishov","year":"2002","journal-title":"J. Virol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1006\/excr.1996.0353","article-title":"The nuclear domain 10 (ND10) is disrupted by the human cytomegalovirus gene product IE1","volume":"229","author":"Korioth","year":"1996","journal-title":"Exp. Cell Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"e02049-16","DOI":"10.1128\/JVI.02049-16","article-title":"The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-Mediated Intrinsic Immunity via the Inhibition of PML De Novo SUMOylation","volume":"91","author":"Schilling","year":"2017","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6517","DOI":"10.1128\/jvi.71.9.6517-6525.1997","article-title":"Primary structure of the alcelaphine herpesvirus 1 genome","volume":"71","author":"Ensser","year":"1997","journal-title":"J. Virol."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Full, F., Jungnickl, D., Reuter, N., Bogner, E., Brulois, K., Scholz, B., Sturzl, M., Myoung, J., Jung, J.U., and Stamminger, T. (2014). Kaposi\u2019s sarcoma associated herpesvirus tegument protein ORF75 is essential for viral lytic replication and plays a critical role in the antagonization of ND10-instituted intrinsic immunity. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1003863"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1128\/JVI.06992-11","article-title":"Herpesvirus saimiri antagonizes nuclear domain 10-instituted intrinsic immunity via an ORF3-mediated selective degradation of cellular protein Sp100","volume":"86","author":"Full","year":"2012","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"8013","DOI":"10.1128\/JVI.01181-16","article-title":"Viral FGARAT Homolog ORF75 of Rhesus Monkey Rhadinovirus Effects Proteasomal Degradation of the ND10 Components SP100 and PML","volume":"90","author":"Hahn","year":"2016","journal-title":"J. Virol."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Tsai, K., Thikmyanova, N., Wojcechowskyj, J.A., Delecluse, H.J., and Lieberman, P.M. (2011). EBV tegument protein BNRF1 disrupts DAXX-ATRX to activate viral early gene transcription. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002376"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.molcel.2015.01.036","article-title":"Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production","volume":"58","author":"He","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1128\/JVI.01980-15","article-title":"Emerging Roles of Protein Deamidation in Innate Immune Signaling","volume":"90","author":"Zhao","year":"2016","journal-title":"J. Virol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1016\/j.chom.2016.10.011","article-title":"A Viral Deamidase Targets the Helicase Domain of RIG-I to Block RNA-Induced Activation","volume":"20","author":"Zhao","year":"2016","journal-title":"Cell Host Microbe."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Clynes, D., Jelinska, C., Xella, B., Ayyub, H., Scott, C., Mitson, M., Taylor, S., Higgs, D.R., and Gibbons, R.J. (2015). Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX. Nat. Commun.","DOI":"10.1038\/ncomms8538"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Wang, Z., Deng, Z., Tutton, S., and Lieberman, P.M. (2017). The Telomeric Response to Viral Infection. Viruses, 9.","DOI":"10.3390\/v9080218"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Merkl, P.E., Orzalli, M.H., and Knipe, D.M. (2018). Mechanisms of Host IFI16, PML, and Daxx Protein Restriction of Herpes Simplex Virus 1 Replication. J. Virol.","DOI":"10.1128\/JVI.00057-18"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/j.molcel.2018.07.034","article-title":"Non-canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-kappaB Signaling after Nuclear DNA Damage","volume":"71","author":"Dunphy","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1242\/jcs.176446","article-title":"Identification of RNF168 as a PML nuclear body regulator","volume":"129","author":"Shire","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"9512","DOI":"10.1128\/JVI.78.17.9512-9523.2004","article-title":"Human cytomegalovirus tegument proteins ppUL82 (pp71) and ppUL35 interact and cooperatively activate the major immediate-early enhancer","volume":"78","author":"Schierling","year":"2004","journal-title":"J. Virol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.virol.2011.03.013","article-title":"Nuclear body formation and PML body remodeling by the human cytomegalovirus protein UL35","volume":"414","author":"Salsman","year":"2011","journal-title":"Virology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1128\/JVI.05442-11","article-title":"Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response","volume":"86","author":"Salsman","year":"2012","journal-title":"J. Virol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Schilling, M., Bulli, L., Weigang, S., Graf, L., Naumann, S., Patzina, C., Wagner, V., Bauersfeld, L., Goujon, C., and Hengel, H. (2018). Human MxB Protein Is a Pan-herpesvirus Restriction Factor. J. Virol.","DOI":"10.1128\/JVI.01056-18"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/nature12653","article-title":"MX2 is an interferon-induced inhibitor of HIV-1 infection","volume":"502","author":"Kane","year":"2013","journal-title":"Nature"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature12542","article-title":"Human MX2 is an interferon-induced post-entry inhibitor of HIV-1 infection","volume":"502","author":"Goujon","year":"2013","journal-title":"Nature"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Crameri, M., Bauer, M., Caduff, N., Walker, R., Steiner, F., Franzoso, F.D., Gujer, C., Boucke, K., Kucera, T., and Zbinden, A. (2018). MxB is an interferon-induced restriction factor of human herpesviruses. Nat. Commun.","DOI":"10.1038\/s41467-018-04379-2"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.virol.2018.07.017","article-title":"MXB inhibits murine cytomegalovirus","volume":"522","author":"Bahr","year":"2018","journal-title":"Virology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/9\/1408\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:17:33Z","timestamp":1760188653000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/8\/9\/1408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,7]]},"references-count":133,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["jcm8091408"],"URL":"https:\/\/doi.org\/10.3390\/jcm8091408","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,7]]}}}