{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T14:24:25Z","timestamp":1774794265853,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,2]],"date-time":"2022-08-02T00:00:00Z","timestamp":1659398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region \u00d6sterg\u00f6tland","award":["ALF-LIU-934451"],"award-info":[{"award-number":["ALF-LIU-934451"]}]},{"name":"Region \u00d6sterg\u00f6tland","award":["ALF-KI-K23003073"],"award-info":[{"award-number":["ALF-KI-K23003073"]}]},{"name":"Region \u00d6sterg\u00f6tland","award":["2018-02862"],"award-info":[{"award-number":["2018-02862"]}]},{"name":"Karolinska Institute","award":["ALF-LIU-934451"],"award-info":[{"award-number":["ALF-LIU-934451"]}]},{"name":"Karolinska Institute","award":["ALF-KI-K23003073"],"award-info":[{"award-number":["ALF-KI-K23003073"]}]},{"name":"Karolinska Institute","award":["2018-02862"],"award-info":[{"award-number":["2018-02862"]}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["ALF-LIU-934451"],"award-info":[{"award-number":["ALF-LIU-934451"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["ALF-KI-K23003073"],"award-info":[{"award-number":["ALF-KI-K23003073"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["2018-02862"],"award-info":[{"award-number":["2018-02862"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Norovirus is the most common cause of acute non-bacterial gastroenteritis. Immunocompromised patients can become chronically infected, with or without symptoms. In Europe, common variable immunodeficiency (CVID) is one of the most common inborn errors of immunity. A potentially severe complication is CVID-associated enteropathy, a disorder with similar histopathology to celiac disease. Studies suggest that chronic norovirus infection may be a contributor to CVID enteropathy, and that the antiviral drug ribavirin can be effective against norovirus. Here, a patient with CVID-like disease with combined B- and T-cell deficiency, had chronic norovirus infection and enteropathy. The patient was routinely administered subcutaneous and intravenous immunoglobulin replacement therapy (SCIg and IVIg). The patient was also administered ribavirin for ~7.5 months to clear the infection. Stool samples (collected 2013\u20132016) and archived paraffin embedded duodenal biopsies were screened for norovirus by qPCR, confirming a chronic infection. Norovirus genotyping was done in 25 stool samples. For evolutionary analysis, the capsid (VP1) and polymerase (RdRp) genes were sequenced in 10 and 12 stool samples, respectively, collected before, during, and after ribavirin treatment. Secretor phenotyping was done in saliva, and serum was analyzed for histo-blood group antigen (HBGA) blocking titers. The chronic norovirus strain formed a unique variant subcluster, with GII.4 Den Haag [P4] variant, circulating around 2009, as the most recent common ancestor. This corresponded to the documented debut of symptoms. The patient was a secretor and had HBGA blocking titers associated with protection in immunocompetent individuals. Several unique amino acid substitutions were detected in immunodominant epitopes of VP1. However, HBGA binding sites were conserved. Ribavirin failed in treating the infection and no clear association between ribavirin-levels and quantity of norovirus shedding was observed. In conclusion, long term infection with norovirus in a patient with severe CVID led to the evolution of a unique norovirus strain with amino acid substitutions in immunodominant epitopes, but conservation within HBGA binding pockets. Regularly administered SCIg, IVIg, and ~7.5-month ribavirin treatment failed to clear the infection.<\/jats:p>","DOI":"10.3390\/v14081708","type":"journal-article","created":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T00:15:26Z","timestamp":1659485726000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Long Term Norovirus Infection in a Patient with Severe Common Variable Immunodeficiency"],"prefix":"10.3390","volume":"14","author":[{"given":"Loa","family":"Ottosson","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie","family":"Hagbom","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rikard","family":"Svernl\u00f6v","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-4966","authenticated-orcid":false,"given":"Sofia","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"},{"name":"Department of Clinical Immunology and Transfusion Medicine and Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatrice","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattias","family":"\u00d6man","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magnus","family":"Str\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lennart","family":"Svensson","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"},{"name":"Division of Infectious Diseases, Department of Medicine, Karolinska Institute, 17111 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5719-5601","authenticated-orcid":false,"given":"\u00c5sa","family":"Nilsdotter-Augustinsson","sequence":"additional","affiliation":[{"name":"Infectious Diseases\/Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-2569","authenticated-orcid":false,"given":"Johan","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/S1473-3099(14)70767-4","article-title":"Global prevalence of norovirus in cases of gastroenteritis: A systematic review and meta-analysis","volume":"14","author":"Ahmed","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","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_3","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/infdis\/jir039","article-title":"Norovirus GII-4 causes a more severe gastroenteritis than other noroviruses in young children","volume":"203","author":"Huhti","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_4","first-page":"185","article-title":"Molecular epidemiology of noroviruses associated with acute sporadic gastroenteritis in children: Global distribution of genogroups, genotypes and GII.4 variants","volume":"56","author":"Trainor","year":"2013","journal-title":"J. Clin. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.meegid.2017.10.001","article-title":"Pediatric norovirus GII.4 infections in Nicaragua, 1999\u20132015","volume":"55","author":"Bucardo","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/infdis\/jiab316","article-title":"Secretor status strongly influences the incidence of symptomatic norovirus infection in a genotype-dependent manner in a Nicaraguan birth cohort","volume":"225","author":"Reyes","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e02202-19","DOI":"10.1128\/mBio.02202-19","article-title":"Population Genomics of GII.4 Noroviruses Reveal Complex Diversification and New Antigenic Sites Involved in the Emergence of Pandemic Strains","volume":"10","author":"Tohma","year":"2019","journal-title":"mBio"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mallory, M.L., Lindesmith, L.C., Graham, R.L., and Baric, R.S. (2019). GII.4 Human Norovirus: Surveying the Antigenic Landscape. Viruses, 11.","DOI":"10.3390\/v11020177"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7414","DOI":"10.1128\/JVI.06729-11","article-title":"Multiple antigenic sites are involved in blocking the interaction of GII.4 norovirus capsid with ABH histo-blood group antigens","volume":"86","author":"Parra","year":"2012","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Lindesmith, L.C., Beltramello, M., Donaldson, E.F., Corti, D., Swanstrom, J., Debbink, K., Lanzavecchia, A., and Baric, R.S. (2012). Immunogenetic mechanisms driving norovirus GII.4 antigenic variation. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002705"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Debbink, K., Lindesmith, L.C., Donaldson, E.F., and Baric, R.S. (2012). Norovirus immunity and the great escape. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002921"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e00518-17","DOI":"10.1128\/mSphere.00518-17","article-title":"Conformational Occlusion of Blockade Antibody Epitopes, a Novel Mechanism of GII.4 Human Norovirus Immune Evasion","volume":"3","author":"Lindesmith","year":"2018","journal-title":"mSphere"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"van Loben Sels, J.M., and Green, K.Y. (2019). The Antigenic Topology of Norovirus as Defined by B and T Cell Epitope Mapping: Implications for Universal Vaccines and Therapeutics. Viruses, 11.","DOI":"10.3390\/v11050432"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Allen, D.J., Gray, J.J., Gallimore, C.I., Xerry, J., and Iturriza-Gomara, M. (2008). Analysis of amino acid variation in the P2 domain of the GII-4 norovirus VP1 protein reveals putative variant-specific epitopes. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001485"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.3389\/fmicb.2018.00371","article-title":"Intrahost Norovirus Evolution in Chronic Infection Over 5 Years of Shedding in a Kidney Transplant Recipient","volume":"9","author":"Steyer","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8635","DOI":"10.1128\/JVI.00848-11","article-title":"Structural analysis of histo-blood group antigen binding specificity in a norovirus GII.4 epidemic variant: Implications for epochal evolution","volume":"85","author":"Shanker","year":"2011","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1128\/JVI.02968-14","article-title":"Human noroviruses\u2019 fondness for histo-blood group antigens","volume":"89","author":"Singh","year":"2015","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Nordgren, J., and Svensson, L. (2019). Genetic Susceptibility to Human Norovirus Infection: An Update. Viruses, 11.","DOI":"10.3390\/v11030226"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Croci, R., Pezzullo, M., Tarantino, D., Milani, M., Tsay, S.C., Sureshbabu, R., Tsai, Y.J., Mastrangelo, E., Rohayem, J., and Bolognesi, M. (2014). Structural bases of norovirus RNA dependent RNA polymerase inhibition by novel suramin-related compounds. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091765"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12111","DOI":"10.1128\/JVI.00560-07","article-title":"Interferons and ribavirin effectively inhibit Norwalk virus replication in replicon-bearing cells","volume":"81","author":"Chang","year":"2007","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.virol.2012.01.016","article-title":"Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase in complex with 2-thiouridine or ribavirin","volume":"426","author":"Alam","year":"2012","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/ajg.2014.432","article-title":"The role of chronic norovirus infection in the enteropathy associated with common variable immunodeficiency","volume":"110","author":"Woodward","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"170","DOI":"10.2174\/1389200218666170912161449","article-title":"Therapeutics and Immunoprophylaxis Against Noroviruses and Rotaviruses: The Past, Present, and Future","volume":"19","author":"Ghosh","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"van Kampen, J.J.A., Dalm, V., Fraaij, P.L.A., Oude Munnink, B.B., Schapendonk, C.M.E., Izquierdo-Lara, R.W., Villabruna, N., Ettayebi, K., Estes, M.K., and Koopmans, M.P.G. (2022). Clinical and in-vitro evidence favoring immunoglobulin treatment of a chronic norovirus infection in a patient with common variable immunodeficiency. J. Infect. Dis.","DOI":"10.1093\/infdis\/jiac085"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.virusres.2016.12.018","article-title":"Structure(s), function(s), and inhibition of the RNA-dependent RNA polymerase of noroviruses","volume":"234","author":"Deval","year":"2017","journal-title":"Virus Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1128\/JCM.00061-17","article-title":"Slow Clearance of Norovirus following Infection with Emerging Variants of Genotype GII.4 Strains","volume":"55","author":"Gustavsson","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cei.12884","article-title":"Chronic norovirus infection and common variable immunodeficiency","volume":"188","author":"Woodward","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1099\/vir.0.005082-0","article-title":"Quasispecies dynamics and molecular evolution of human norovirus capsid P region during chronic infection","volume":"90","author":"Carlsson","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/tid.12472","article-title":"Prolonged norovirus infection after pancreas transplantation: A case report and review of chronic norovirus","volume":"18","author":"Echenique","year":"2016","journal-title":"Transpl. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e2049","DOI":"10.1002\/rmv.2049","article-title":"Viral infection in primary antibody deficiency syndromes","volume":"29","author":"Jones","year":"2019","journal-title":"Rev. Med. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/S0140-6736(08)61199-X","article-title":"Common variable immunodeficiency: A new look at an old disease","volume":"372","author":"Park","year":"2008","journal-title":"Lancet"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1038\/ajg.2010.214","article-title":"The enteropathy associated with common variable immunodeficiency: The delineated frontiers with celiac disease","volume":"105","author":"Malamut","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7244","DOI":"10.1128\/JVI.00203-14","article-title":"Within-host evolution results in antigenically distinct GII.4 noroviruses","volume":"88","author":"Debbink","year":"2014","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3389\/fmicb.2020.00375","article-title":"Intra-Host Evolution of Norovirus GII.4 in a Chronic Infected Patient with Hematopoietic Stem Cell Transplantation","volume":"11","author":"Yu","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_35","first-page":"S255","article-title":"Nitazoxanide is effective therapy for norovirus gastroenteritis after chemotherapy and hematopoietic stem cell transplantation (HSCT)","volume":"21","author":"Morris","year":"2015","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12560-019-09410-3","article-title":"Secretor Status is Associated with Susceptibility to Disease in a Large GII.6 Norovirus Foodborne Outbreak","volume":"12","author":"Sharma","year":"2019","journal-title":"Food Environ. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00567-17","DOI":"10.1128\/JVI.00567-17","article-title":"Human Sera Collected between 1979 and 2010 Possess Blocking-Antibody Titers to Pandemic GII.4 Noroviruses Isolated over Three Decades","volume":"91","author":"Sharma","year":"2017","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1128\/CVI.00196-15","article-title":"Serological Correlates of Protection against a GII.4 Norovirus","volume":"22","author":"Atmar","year":"2015","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"11056","DOI":"10.1128\/JVI.01333-14","article-title":"Deep sequencing of norovirus genomes defines evolutionary patterns in an urban tropical setting","volume":"88","author":"Cotten","year":"2014","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3201\/eid1601.090633","article-title":"Norovirus gastroenteritis outbreak with a secretor-independent susceptibility pattern, Sweden","volume":"16","author":"Nordgren","year":"2010","journal-title":"Emerg. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e1926","DOI":"10.1002\/rmv.1926","article-title":"Norovirus infection in primary immune deficiency","volume":"27","author":"Brown","year":"2017","journal-title":"Rev. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5756","DOI":"10.1128\/JVI.03063-14","article-title":"What is the reservoir of emergent human norovirus strains?","volume":"89","author":"Karst","year":"2015","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1002\/jmv.24559","article-title":"Recent advances in understanding norovirus pathogenesis","volume":"88","author":"Karst","year":"2016","journal-title":"J. Med. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"648","DOI":"10.14309\/ajg.0000000000000140","article-title":"A High Prevalence of Gastrointestinal Manifestations in Common Variable Immunodeficiency","volume":"114","author":"Pikkarainen","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.diagmicrobio.2018.08.002","article-title":"Chronic norovirus infection in primary immune deficiency disorders: An international case series","volume":"93","author":"Rolfes","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1093\/cid\/ciw060","article-title":"Norovirus Infections Occur in B-Cell-Deficient Patients","volume":"62","author":"Brown","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1086\/653939","article-title":"Chronic norovirus infection after kidney transplantation: Molecular evidence for immune-driven viral evolution","volume":"51","author":"Schorn","year":"2010","journal-title":"Clin. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1128\/JVI.06712-11","article-title":"Contribution of intra- and interhost dynamics to norovirus evolution","volume":"86","author":"Bull","year":"2012","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Garaicoechea, L., Aguilar, A., Parra, G.I., Bok, M., Sosnovtsev, S.V., Canziani, G., Green, K.Y., Bok, K., and Parreno, V. (2015). Llama nanoantibodies with therapeutic potential against human norovirus diarrhea. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133665"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/1743-422X-6-150","article-title":"Characterisation of a GII-4 norovirus variant-specific surface-exposed site involved in antibody binding","volume":"6","author":"Allen","year":"2009","journal-title":"Virol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1128\/JVI.06189-11","article-title":"Genetic mapping of a highly variable norovirus GII.4 blockade epitope: Potential role in escape from human herd immunity","volume":"86","author":"Debbink","year":"2012","journal-title":"J. Virol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"vex018","DOI":"10.1093\/ve\/vex018","article-title":"Persistent infections in immunocompromised hosts are rarely sources of new pathogen variants","volume":"3","author":"Eden","year":"2017","journal-title":"Virus Evol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00352-16","DOI":"10.1128\/mSphere.00352-16","article-title":"Human Norovirus Evolution in a Chronically Infected Host","volume":"2","author":"Doerflinger","year":"2017","journal-title":"mSphere"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.tim.2017.03.003","article-title":"Short-Sighted Virus Evolution and a Germline Hypothesis for Chronic Viral Infections","volume":"25","author":"Lythgoe","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Davis, A., Cortez, V., Grodzki, M., Dallas, R., Ferrolino, J., Freiden, P., Maron, G., Hakim, H., Hayden, R.T., and Tang, L. (2020). Infectious Norovirus Is Chronically Shed by Immunocompromised Pediatric Hosts. Viruses, 12.","DOI":"10.3390\/v12060619"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4843","DOI":"10.1128\/JVI.03223-15","article-title":"Structural Basis for Norovirus Inhibition by Human Milk Oligosaccharides","volume":"90","author":"Weichert","year":"2016","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1708\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:01:27Z","timestamp":1760140887000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/8\/1708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,2]]},"references-count":56,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["v14081708"],"URL":"https:\/\/doi.org\/10.3390\/v14081708","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,2]]}}}