{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:42:55Z","timestamp":1760233375179,"version":"build-2065373602"},"reference-count":77,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Cooperative Research Program of the Ministry of Food and Drug Safety, Republic of Korea","award":["14162MFDS973"],"award-info":[{"award-number":["14162MFDS973"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Norovirus genogroup II (NoV GII) induces acute gastrointestinal food-borne illness in humans. Because gnotobiotic pigs can be infected with human norovirus (HuNoV) GII, they are frequently used to analyze the associated pathogenic mechanisms and immune responses, which remain poorly understood. Recently, mRNA sequencing analysis (RNA-Seq) has been used to identify cellular responses to viruses. In this study, we investigated the host immune response and possible mechanisms involved in virus evasion in the ileum of gnotobiotic pigs infected with HuNoV by RNA-Seq. HuNoV was detected in the feces, blood, and tissues of the jejunum, ileum, colon, mesenteric lymph node, and spleen of pigs infected with HuNoV. In analysis of mRNA sequencing, expression of anti-viral protein genes such as OAS1, MX1, and MX2 were largely decreased, whereas type I IFN was increased in pigs infected with HuNoV. In addition, expression of TNF and associated anti-inflammatory cytokine genes such as IL10 was increased in HuNoV-infected pigs. Expression of genes related to natural killer (NK) cell cytotoxicity and CD8+ T cell exhaustion was increased, whereas that of MHC class I genes was decreased. Expression profiles of selected genes were further confirmed by qRT-PCR and Western blot. These results suggest that infection with HuNoV induces NK cell-mediated cytotoxicity but suppresses type I IFN- and CD8+ T cell-mediated antiviral responses.<\/jats:p>","DOI":"10.3390\/v13010092","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T20:32:47Z","timestamp":1610397167000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Analysis of the Immune Responses in the Ileum of Gnotobiotic Pigs Infected with the Recombinant GII.p12_GII.3 Human Norovirus by mRNA Sequencing"],"prefix":"10.3390","volume":"13","author":[{"given":"Byung-Joo","family":"Park","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Seop","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Hoon","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon-Jeong","family":"Go","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Hwi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7730-8538","authenticated-orcid":false,"given":"Changsun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong, Gyeonggi 17546, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7049-5510","authenticated-orcid":false,"given":"Soontag","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, College of Biotechnology and Natural Resources, Chung-Ang University, Anseong, Gyeonggi 17546, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinjong","family":"Myoung","sequence":"additional","affiliation":[{"name":"Korea Zoonosis Research Institute, Chonbuk National University, Jeonju, Jeollabuk-do 54896, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joong-Bok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Yong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4158-6402","authenticated-orcid":false,"given":"Chang-Seon","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Won","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hoon-Taek","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Biotechnology, Konkuk University, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"In-Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, Konkuk University, Gwangjin-gu, Seoul 05029, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1128\/CMR.00075-14","article-title":"Norovirus","volume":"28","author":"Robilotti","year":"2015","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.3201\/eid1908.130465","article-title":"Norovirus disease in the United States","volume":"19","author":"Hall","year":"2013","journal-title":"Emerg. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1128\/JCM.01535-14","article-title":"Advances in laboratory methods for detection and typing of norovirus","volume":"53","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1099\/jgv.0.001318","article-title":"Updated classification of norovirus genogroups and genotypes","volume":"100","author":"Chhabra","year":"2019","journal-title":"J. Gen. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Siebenga, J.J., Lemey, P., Pond, S.L.K., Rambaut, A., Vennema, H., and Koopmans, M. (2010). Phylodynamic reconstruction reveals norovirus GII. 4 epidemic expansions and their molecular determinants. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000884"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1099\/vir.0.19478-0","article-title":"Laboratory efforts to cultivate noroviruses","volume":"85","author":"Duizer","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1038\/nprot.2015.121","article-title":"Human norovirus culture in B cells","volume":"10","author":"Jones","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1099\/jgv.0.000545","article-title":"Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients","volume":"97","author":"Karandikar","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/cei.12681","article-title":"Human norovirus infection and the acute serum cytokine response","volume":"182","author":"Newman","year":"2015","journal-title":"Clin. Exp. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1128\/JVI.01306-06","article-title":"Binding patterns of human norovirus-like particles to buccal and intestinal tissues of gnotobiotic pigs in relation to A\/H histo-blood group antigen expression","volume":"81","author":"Cheetham","year":"2007","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10372","DOI":"10.1128\/JVI.00809-06","article-title":"Pathogenesis of a genogroup II human norovirus in gnotobiotic pigs","volume":"80","author":"Cheetham","year":"2006","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.1099\/vir.0.054080-0","article-title":"Median infectious dose of human norovirus GII. 4 in gnotobiotic pigs is decreased by simvastatin treatment and increased by age","volume":"94","author":"Bui","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.4014\/jmb.1810.09061","article-title":"Pathogenesis of human norovirus genogroup II genotype 4 in post-weaning gnotobiotic pigs","volume":"28","author":"Park","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9183","DOI":"10.1128\/JVI.00558-07","article-title":"Cytokine and antibody responses in gnotobiotic pigs after infection with human norovirus genogroup II. 4 (HS66 strain)","volume":"81","author":"Souza","year":"2007","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"25222","DOI":"10.1038\/srep25222","article-title":"Increased and prolonged human norovirus infection in RAG2\/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency","volume":"6","author":"Lei","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1126\/science.1077905","article-title":"STAT1-dependent innate immunity to a Norwalk-like virus","volume":"299","author":"Karst","year":"2003","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1099\/vir.0.042176-0","article-title":"Development of a reverse-genetics system for murine norovirus 3: Long-term persistence occurs in the caecum and colon","volume":"93","author":"Arias","year":"2012","journal-title":"J. Gen. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1126\/science.1258025","article-title":"Commensal microbes and interferon-\u03bb determine persistence of enteric murine norovirus infection","volume":"347","author":"Baldridge","year":"2015","journal-title":"Science"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1128\/JVI.02096-06","article-title":"Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses","volume":"81","author":"Mumphrey","year":"2007","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1038\/s41564-017-0057-7","article-title":"The major targets of acute norovirus infection are immune cells in the gut-associated lymphoid tissue","volume":"2","author":"Grau","year":"2017","journal-title":"Nat. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1126\/science.aar3799","article-title":"Tropism for tuft cells determines immune promotion of norovirus pathogenesis","volume":"360","author":"Wilen","year":"2018","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wobus, C.E., Karst, S.M., Thackray, L.B., Chang, K.-O., Sosnovtsev, S.V., Belliot, G., Krug, A., Mackenzie, J.M., Green, K.Y., and Virgin, H.W. (2004). Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol., 2.","DOI":"10.1371\/journal.pbio.0020432"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Chachu, K.A., LoBue, A.D., Strong, D.W., Baric, R.S., and Virgin, H.W. (2008). Immune mechanisms responsible for vaccination against and clearance of mucosal and lymphatic norovirus infection. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000236"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nice, T.J., Osborne, L.C., Tomov, V.T., Artis, D., Wherry, E.J., and Virgin, H.W. (2016). Type I interferon receptor deficiency in dendritic cells facilitates systemic murine norovirus persistence despite enhanced adaptive immunity. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005684"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Zhu, S., Regev, D., Watanabe, M., Hickman, D., Moussatche, N., Jesus, D.M., Kahan, S.M., Napthine, S., Brierley, I., and Hunter, R.N. (2013). Identification of immune and viral correlates of norovirus protective immunity through comparative study of intra-cluster norovirus strains. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003592"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3389\/fimmu.2017.00959","article-title":"RNA sequencing of murine norovirus-infected cells reveals transcriptional alteration of genes important to viral recognition and antigen presentation","volume":"8","author":"Netzler","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01385-19","DOI":"10.1128\/MRA.01385-19","article-title":"Coding-complete genome sequence of a recombinant human norovirus strain identified as subtype GII.p12_GII.3","volume":"9","author":"Park","year":"2020","journal-title":"Microbiol. Resour. Announc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1002\/jmv.24991","article-title":"Experimental miniature piglet model for the infection of human norovirus GII","volume":"90","author":"Seo","year":"2018","journal-title":"J. Med. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1128\/JCM.41.4.1548-1557.2003","article-title":"Broadly reactive and highly sensitive assay for Norwalk-like viruses based on real-time quantitative reverse transcription-PCR","volume":"41","author":"Kageyama","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2004.08.023","article-title":"Real-time RT-PCR for norovirus screening in shellfish","volume":"123","author":"Loisy","year":"2005","journal-title":"J. Virol. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: Discovering splice junctions with RNA-Seq","volume":"25","author":"Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/gb-2004-5-10-r80","article-title":"Bioconductor: Open software development for computational biology and bioinformatics","volume":"5","author":"Gentleman","year":"2004","journal-title":"Genome Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal analysis approaches in ingenuity pathway analysis","volume":"30","author":"Green","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"658","DOI":"10.4014\/jmb.1901.01067","article-title":"Immunocontraceptive effects in male rats vaccinated with gonadotropin-releasing hormone-I and-II protein complex","volume":"29","author":"Kim","year":"2019","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.3201\/eid1410.080117","article-title":"Norwalk virus shedding after experimental human infection","volume":"14","author":"Atmar","year":"2008","journal-title":"Emerg. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Karst, S.M., and Wobus, C.E. (2015). A working model of how noroviruses infect the intestine. PLoS Pathog., 11.","DOI":"10.1371\/journal.ppat.1004626"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"957","DOI":"10.3945\/jn.110.132134","article-title":"Vitamin A modifies the intestinal chemokine and cytokine responses to norovirus infection in Mexican children","volume":"141","author":"Long","year":"2011","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1128\/JVI.01347-07","article-title":"Pathogenesis and immune responses in gnotobiotic calves after infection with the genogroup II. 4-HS66 strain of human norovirus","volume":"82","author":"Souza","year":"2008","journal-title":"J. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1097\/01.MIB.0000441346.86827.ed","article-title":"Norovirus triggered microbiota-driven mucosal inflammation in interleukin 10-deficient mice","volume":"20","author":"Basic","year":"2014","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9237","DOI":"10.1073\/pnas.161293498","article-title":"Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition","volume":"98","author":"Bauer","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1126\/science.282.5396.2085","article-title":"Defective LPS signaling in C3H\/HeJ and C57BL\/10ScCr mice: Mutations in Tlr4 gene","volume":"282","author":"Poltorak","year":"1998","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.virol.2008.07.002","article-title":"Hantaan virus induces toll-like receptor 4 expression, leading to enhanced production of beta interferon, interleukin-6 and tumor necrosis factor-alpha","volume":"380","author":"Jiang","year":"2008","journal-title":"Virology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e46182","DOI":"10.15252\/embr.201846182","article-title":"Infection with the dengue RNA virus activates TLR9 signaling in human dendritic cells","volume":"19","author":"Lai","year":"2018","journal-title":"EMBO Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/43213","article-title":"A new protein containing an SH2 domain that inhibits JAK kinases","volume":"387","author":"Endo","year":"1997","journal-title":"Nature"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6405","DOI":"10.3892\/mmr.2017.7384","article-title":"Downregulated SOCS1 expression activates the JAK1\/STAT1 pathway and promotes polarization of macrophages into M1 type","volume":"16","author":"Liang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1126\/science.1258100","article-title":"Interferon-\u03bb cures persistent murine norovirus infection in the absence of adaptive immunity","volume":"347","author":"Nice","year":"2015","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/S0952-7915(98)80168-4","article-title":"Natural killer cell receptors","volume":"10","author":"Yokoyama","year":"1998","journal-title":"Curr. Opin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1084\/jem.20070695","article-title":"Differential natural killer cell\u2013mediated inhibition of HIV-1 replication based on distinct KIR\/HLA subtypes","volume":"204","author":"Alter","year":"2007","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/1521-4141(200002)30:2<509::AID-IMMU509>3.0.CO;2-H","article-title":"A role for MHC class I down-regulation in NK cell lysis of herpes virus-infected cells","volume":"30","author":"Huard","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng934","article-title":"Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS","volume":"31","author":"Martin","year":"2002","journal-title":"Nat. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1399-0039.2006.773_4.x","article-title":"Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C ligands on resolving hepatitis C virus infection","volume":"69","author":"Rauch","year":"2007","journal-title":"Tissue Antigens"},{"key":"ref_54","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_55","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/cid\/ciw060","article-title":"Norovirus infections occur in B-cell\u2013deficient patients","volume":"62","author":"Brown","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.virusres.2019.05.002","article-title":"Infectivity of GII. 4 human norovirus does not differ between TB-NK+ severe combined immunodeficiency (SCID) and non-SCID gnotobiotic pigs, implicating the role of NK cells in mediation of human norovirus infection","volume":"267","author":"Annamalai","year":"2019","journal-title":"Virus Res."},{"key":"ref_57","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_58","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_59","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1146\/annurev.immunol.17.1.189","article-title":"Natural killer cells in antiviral defense: Function and regulation by innate cytokines","volume":"17","author":"Biron","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.4049\/jimmunol.170.3.1249","article-title":"Critical role of MHC class I-related chain A and B expression on IFN-\u03b1-stimulated dendritic cells in NK cell activation: Impairment in chronic hepatitis C virus infection","volume":"170","author":"Jinushi","year":"2003","journal-title":"J. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13790","DOI":"10.1073\/pnas.250483097","article-title":"MHC I-dependent antigen presentation is inhibited by poliovirus protein 3A","volume":"97","author":"Deitz","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7999","DOI":"10.1158\/0008-5472.CAN-05-4399","article-title":"Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma","volume":"66","author":"Sengupta","year":"2006","journal-title":"Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1073\/pnas.89.5.1890","article-title":"Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes","volume":"89","author":"Rousset","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1271\/bbb.68.2279","article-title":"IL-10 augments antibody production in in vitro immunized lymphocytes by inducing a Th2-type response and B cell maturation","volume":"68","author":"Xu","year":"2004","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bengsch, B., Seigel, B., Ruhl, M., Timm, J., Kuntz, M., Blum, H.E., Pircher, H., and Thimme, R. (2010). Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000947"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1084\/jem.20132577","article-title":"Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection","volume":"211","author":"Kamphorst","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.immuni.2017.09.017","article-title":"Differentiation and protective capacity of virus-specific CD8+ T cells suggest murine norovirus persistence in an immune-privileged enteric niche","volume":"47","author":"Tomov","year":"2017","journal-title":"Immunity"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10514","DOI":"10.1128\/JVI.79.16.10514-10527.2005","article-title":"Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection","volume":"79","author":"Brooks","year":"2005","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13878","DOI":"10.1073\/pnas.251539598","article-title":"High-level HIV-1 viremia suppresses viral antigen-specific CD4+ T cell proliferation","volume":"98","author":"McNeil","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Nakamoto, N., Cho, H., Shaked, A., Olthoff, K., Valiga, M.E., Kaminski, M., Gostick, E., Price, D.A., Freeman, G.J., and Wherry, E.J. (2009). Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1\/CTLA-4 blockade. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000313"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1002\/hep.24249","article-title":"Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection","volume":"53","author":"Schurich","year":"2011","journal-title":"Hepatology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.meegid.2016.04.017","article-title":"Human norovirus hyper-mutation revealed by ultra-deep sequencing","volume":"41","author":"Cuevas","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s41586-020-2922-4","article-title":"A molecular cell atlas of the human lung from single cell RNA sequencing","volume":"587","author":"Travaglini","year":"2020","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Liu, T., Jia, P., Fang, B., and Zhao, Z. (2020). Differential expression of viral transcripts from single-cell RNA sequencing of moderate and severe COVID-19 patients and its implications for case severity. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.603509"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2962","DOI":"10.1016\/j.csbj.2020.10.016","article-title":"Probing infectious disease by single-cell RNA sequencing: Progresses and perspectives","volume":"18","author":"Luo","year":"2020","journal-title":"Comput. Struct. Biotechnol. J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/92\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:09:52Z","timestamp":1760159392000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/1\/92"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["v13010092"],"URL":"https:\/\/doi.org\/10.3390\/v13010092","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2021,1,11]]}}}