{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:47:56Z","timestamp":1783457276640,"version":"3.55.0"},"reference-count":81,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T00:00:00Z","timestamp":1539302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Hepatitis C virus (HCV) represents a challenging global health threat to ~200 million infected individuals. Clinical data suggest that only ~10\u201315% of acutely HCV-infected individuals will achieve spontaneous viral clearance despite exuberant virus-specific immune responses, which is largely attributed to difficulties in recognizing the pathognomonic symptoms during the initial stages of exposure to the virus. Given the paucity of a suitable small animal model, it is also equally challenging to study the early phases of viral establishment. Further, the host factors contributing to HCV chronicity in a vast majority of acutely HCV-infected individuals largely remain unexplored. The last few years have witnessed a surge in studies showing that HCV adopts myriad mechanisms to disconcert virus-specific immune responses in the host to establish persistence, which includes, but is not limited to viral escape mutations, viral growth at privileged sites, and antagonism. Here we discuss a few hitherto poorly explained mechanisms employed by HCV that are believed to lead to chronicity in infected individuals. A better understanding of these mechanisms would aid the design of improved therapeutic targets against viral establishment in susceptible individuals.<\/jats:p>","DOI":"10.3390\/cells7100165","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T10:54:03Z","timestamp":1539341643000},"page":"165","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion"],"prefix":"10.3390","volume":"7","author":[{"given":"Muttiah","family":"Barathan","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, LembahPantai, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosmawati","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of Malaya, 50603 LembahPantai, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yean K.","family":"Yong","sequence":"additional","affiliation":[{"name":"Laboratory Center, Xiamen University Malaysia, 43900 Sepang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6107-4228","authenticated-orcid":false,"given":"Meganathan","family":"Kannan","sequence":"additional","affiliation":[{"name":"Division of Blood and Vascular Biology, Department of Life Sciences, Central University of Tamil Nadu (CUTN), Thiruvarur 610005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamuna","family":"Vadivelu","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, LembahPantai, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Saeidi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Malaya, LembahPantai, 50603 Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Larsson","sequence":"additional","affiliation":[{"name":"Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linkoping University, 58 183 Linkoping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7866-9818","authenticated-orcid":false,"given":"Esaki Muthu","family":"Shankar","sequence":"additional","affiliation":[{"name":"Division of Infection Biology and Medical Microbiology, Department of Life Sciences, Central University of Tamil Nadu (CUTN), Thiruvarur 610005, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1038\/emi.2014.19","article-title":"Natural reservoirs for homologs of hepatitis C virus","volume":"3","author":"Pfaender","year":"2014","journal-title":"Emerg. Microbes Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.4254\/wjh.v7.i10.1377","article-title":"Hepatitis C virus: Virology, diagnosis and treatment","volume":"7","author":"Li","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e000042","DOI":"10.1136\/esmoopen-2016-000042","article-title":"Cancer and liver cirrhosis: Implications on prognosis and management","volume":"1","author":"Pinter","year":"2016","journal-title":"ESMO Open"},{"key":"ref_4","first-page":"37","article-title":"Frequency distribution of hepatitis in three districts of Hazara division","volume":"2","author":"Khan","year":"2010","journal-title":"Asian J. Med. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1177\/2040622310384308","article-title":"Pegylated interferon and ribavirin treatment for hepatitis C virus infection","volume":"2","author":"Palumbo","year":"2011","journal-title":"Ther. Adv. Chronic Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1002\/hep.22759","article-title":"American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: An update","volume":"49","author":"Ghany","year":"2009","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1038\/nm.3248","article-title":"Understanding the hepatitis C virus life cycle paves the way for highly effective therapies","volume":"19","author":"Scheel","year":"2013","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.immuni.2013.12.010","article-title":"Immune responses to HCV and other hepatitis viruses","volume":"40","author":"Park","year":"2014","journal-title":"Immunity"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.27259","article-title":"Global distribution and prevalence of hepatitis C virus genotypes","volume":"61","author":"Messina","year":"2015","journal-title":"Hepatology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/00042737-200510000-00013","article-title":"Host immune responses in hepatitis C virus clearance","volume":"17","author":"Barrett","year":"2005","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S25","DOI":"10.1086\/429492","article-title":"Cellular immune responses against hepatitis C virus","volume":"41","author":"Koziel","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3418","DOI":"10.3748\/wjg.v20.i13.3418","article-title":"Adaptive immune response during hepatitis C virus infection","volume":"20","author":"Larrubia","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/sj.cdd.4400823","article-title":"Host defense, viruses and apoptosis","volume":"8","author":"Barber","year":"2001","journal-title":"Cell Death Differ."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1189\/jlb.0705397","article-title":"Viral strategies for evading antiviral cellular immune responses of the host","volume":"79","author":"Iannello","year":"2006","journal-title":"J. Leukoc. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.virol.2005.09.028","article-title":"Viral persistence: Parameters, mechanisms and future predictions","volume":"344","author":"Oldstone","year":"2006","journal-title":"Virology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1096\/fj.02-0537fje","article-title":"Involvement of TRAIL and its receptors in viral hepatitis","volume":"17","author":"Mundt","year":"2003","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Silberstein, E., Ulitzky, L., Lima, L.A., Cehan, N., Teixeira-Carvalho, A., Roingeard, P., and Taylor, D.R. (2016). HCV-mediated apoptosis of hepatocytes in culture and viral pathogenesis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155708"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1002\/hep.25681","article-title":"Hepatocellular carcinoma: Detection with diffusion-weighted versus contrast-enhanced magnetic resonance imaging in pretransplant patients","volume":"56","author":"Park","year":"2012","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1016\/j.jhep.2014.07.010","article-title":"Pathogenesis and prevention of hepatitis C virus-induced hepatocellular carcinoma","volume":"61","author":"Hoshida","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.virol.2005.11.017","article-title":"Apoptosis of activated CD4+ and CD8+ T cells is enhanced by co-culture with hepatocytes expressing hepatitis C virus (HCV) structural proteins through FasL induction","volume":"346","author":"Iken","year":"2006","journal-title":"Virology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/S0168-8278(01)00207-0","article-title":"Enhanced peripheral T-cell apoptosis in chronic hepatitis C virus infection: Association with liver disease severity","volume":"35","author":"Toubi","year":"2001","journal-title":"J. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1007\/s12072-009-9158-6","article-title":"Role of free radicals in liver diseases","volume":"3","author":"Muriel","year":"2009","journal-title":"Hepatol. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.jhep.2013.12.026","article-title":"Biomarkers of liver cell death","volume":"60","author":"Eguchi","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1007\/s10495-014-1084-y","article-title":"Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes","volume":"20","author":"Barathan","year":"2015","journal-title":"Apoptosis"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1742-4933-5-11","article-title":"Immunity, ageing and cancer","volume":"5","author":"Derhovanessian","year":"2008","journal-title":"Immun. Ageing"},{"key":"ref_27","first-page":"1680","article-title":"T cell replicative senescence in human aging","volume":"19","author":"Chou","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2567.2011.03470.x","article-title":"CD8+ CD28\u2212 and CD8+ CD57+ T cells and their role in health and disease","volume":"134","author":"Strioga","year":"2011","journal-title":"Immunology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.mad.2015.09.003","article-title":"The silent war of CMV in aging and HIV infection","volume":"158","author":"Effros","year":"2016","journal-title":"Mech. Ageing Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3244","DOI":"10.1182\/blood-2003-03-0927","article-title":"Phenotypic and functional T-cell aging in rhesus macaques (Macacamulatta): Differential behavior of CD4 and CD8 subsets","volume":"102","author":"Messaoudi","year":"2003","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.it.2009.04.007","article-title":"T-cell immunosenescence: Lessons learned from mouse models of aging","volume":"30","author":"Maue","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_32","first-page":"271","article-title":"Human T cell aging and the impact of persistent viral infections","volume":"4","author":"Larbi","year":"2013","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1128\/CMR.17.4.1012-1030.2004","article-title":"Chronic immune activation associated with chronic helminthic and human immunodeficiency virus infections: Role of hyporesponsiveness and anergy","volume":"17","author":"Borkow","year":"2004","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"8415","DOI":"10.4049\/jimmunol.175.12.8415","article-title":"Functional and phenotypic characterization of CD57+CD4+ T cells and their association with HIV-1-induced T cell dysfunction","volume":"175","author":"Palmer","year":"2005","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.4049\/jimmunol.0900182","article-title":"Differential association of programmed death-1 and CD57 with ex vivo survival of CD8+ T cells in HIV infection","volume":"183","author":"Petrovas","year":"2009","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cellimm.2015.05.005","article-title":"Concurrent loss of co-stimulatory molecules and functional cytokine secretion attributes leads to proliferative senescence of CD8+ T cells in HIV\/TB co-infection","volume":"297","author":"Saeidi","year":"2015","journal-title":"Cell. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1086\/509510","article-title":"Functionally competent antigen-specific CD127 (hi) memory CD8+ T cells are preserved only in HIV-infected individuals receiving early treatment","volume":"195","author":"Sabbaj","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1182\/blood-2003-09-3333","article-title":"Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load","volume":"104","author":"Deeks","year":"2004","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chou, J.P., Ramirez, C.M., Wu, J.E., and Effros, R.B. (2013). Accelerated aging in HIV\/AIDS: Novel biomarkers of senescent human CD8+ T cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064702"},{"key":"ref_40","first-page":"348746","article-title":"The story of CD4+ CD28\u2212 T cells revisited: Solved or still ongoing?","volume":"2015","author":"Maly","year":"2015","journal-title":"J. Immunol. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1189\/jlb.0809566","article-title":"CD57+ T lymphocytes and functional immune deficiency","volume":"87","author":"Focosi","year":"2010","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1080\/21505594.2017.1292197","article-title":"Immunosenescence and hurdles in the clinical management of older HIV-patients","volume":"8","author":"Ripa","year":"2017","journal-title":"Virulence"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/eci.12581","article-title":"Peripheral loss of CD8+ CD161++ TCRV\u03b17\u00b72+ mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients","volume":"46","author":"Barathan","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.4049\/jimmunol.179.6.3543","article-title":"Impaired induction of CD27 and CD28 predicts naive CD4 T cell proliferation defects in HIV disease","volume":"179","author":"Luciano","year":"2007","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1002\/hep.21365","article-title":"Loss of IL-7 receptor alpha-chain (CD127) expression in acute HCV infection associated with viral persistence","volume":"44","author":"Burton","year":"2006","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1002\/rmv.702","article-title":"A spatial view of the CD8+ T-cell response: The case of, H.C.V","volume":"21","author":"Racanelli","year":"2011","journal-title":"Rev. Med. Virol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1016\/j.jhep.2014.07.005","article-title":"Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation","volume":"61","author":"Bengsch","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6697","DOI":"10.4049\/jimmunol.0800997","article-title":"Chronic antigen stimulation alone is sufficient to drive CD8+ T cell exhaustion","volume":"182","author":"Bucks","year":"2009","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","article-title":"Molecular signature of CD8+ T cell exhaustion during chronic viral infection","volume":"27","author":"Wherry","year":"2007","journal-title":"Immunity"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1084\/jem.20041852","article-title":"Repeated stimulation of CD4 effector T cells can limit their protective function","volume":"201","author":"Dibble","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.it.2015.02.008","article-title":"Overcoming T cell exhaustion in infection and cancer","volume":"36","author":"Pauken","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.3389\/fimmu.2017.01215","article-title":"Coinhibitory receptor expression and immune checkpoint blockade: Maintaining a balance in CD8+ T cell responses to chronic viral infections and cancer","volume":"8","author":"Okoye","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.it.2013.10.001","article-title":"Tolerance and exhaustion: Defining mechanisms of T cell dysfunction","volume":"35","author":"Schietinger","year":"2014","journal-title":"Trends Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"869","DOI":"10.3109\/10715762.2013.837577","article-title":"Involvement of free radicals and oxidative stress in NAFLD\/NASH","volume":"47","author":"Sumida","year":"2013","journal-title":"Free Radic. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11398","DOI":"10.1128\/JVI.01177-06","article-title":"Ferrari CPD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion","volume":"80","author":"Urbani","year":"2006","journal-title":"J. Virol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1128\/JVI.02474-07","article-title":"High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome","volume":"82","author":"Kasprowicz","year":"2008","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-2249.2011.04393.x","article-title":"Modulation of CD4+ T cell responses following splenectomy in hepatitis C virus-related liver cirrhosis","volume":"165","author":"Hashimoto","year":"2011","journal-title":"Clin. Exp. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4103\/1110-2098.192444","article-title":"PD-1 expression on peripheral CD8+ T cells closely correlated with hepatitis C virus viral load in chronic hepatitis C patients","volume":"29","author":"Fathy","year":"2016","journal-title":"Menoufia Med. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0016-5085(99)70353-7","article-title":"Recurrence of hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C","volume":"117","author":"Gerlach","year":"1999","journal-title":"Gastroenterology"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1002\/hep.20669","article-title":"Preferential loss of IL-2-secreting CD4+ T helper cells in chronic HCV infection","volume":"41","author":"Semmo","year":"2005","journal-title":"Hepatology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1422","DOI":"10.1053\/j.gastro.2011.07.004","article-title":"Inhibitory molecules that regulate expansion and restoration of HCV-specific CD4+ T cells in patients with chronic infection","volume":"141","author":"Raziorrouh","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellimm.2016.12.002","article-title":"CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides","volume":"313","author":"Barathan","year":"2017","journal-title":"Cell. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6104054","DOI":"10.1155\/2017\/6104054","article-title":"IL-10: A multifunctional cytokine in viral infections","volume":"2017","author":"Rojas","year":"2017","journal-title":"J. Immunol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1038\/cti.2017.5","article-title":"MAIT cells: New guardians of the liver","volume":"6","author":"Kurioka","year":"2017","journal-title":"Clin. Transl. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.3389\/fimmu.2017.01540","article-title":"Mucosal-associated invariant T cells: New insights into antigen recognition and activation","volume":"8","author":"Xiao","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3390\/antib3010016","article-title":"Invariant natural killer T cells","volume":"3","author":"Cianferoni","year":"2014","journal-title":"Antibodies"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nature11605","article-title":"MR1 presents microbial vitamin B metabolites to MAIT cells","volume":"491","author":"Patel","year":"2012","journal-title":"Nature"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.4161\/cc.25706","article-title":"Toward the realization of cell therapy: The advent of MAIT cells from iPSCs","volume":"12","author":"Wakao","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/ni.1890","article-title":"Antimicrobial activity of mucosal-associated invariant T cells","volume":"11","author":"Martin","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1016\/j.micinf.2011.03.007","article-title":"Mucosal associated invariant T cells and the immune response to infection","volume":"13","author":"Gold","year":"2011","journal-title":"Microbes Infect."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"450","DOI":"10.3389\/fimmu.2014.00450","article-title":"Mucosal-associated invariant T-cells: New players in anti-bacterial immunity","volume":"5","author":"Ussher","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1189\/jlb.4RU0216-084R","article-title":"Functional role of mucosal-associated invariant T cells in HIV infection","volume":"100","author":"Saeidi","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.it.2011.02.005","article-title":"Mucosal-associated invariant T cells: Unconventional development and function","volume":"32","author":"Guerri","year":"2011","journal-title":"Trends Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1365-2249.2012.04625.x","article-title":"Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: Are we close to reality?","volume":"171","author":"Simoni","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1038\/ncomms11653","article-title":"MAIT cells are activated during human viral infections","volume":"7","author":"Scherwitzl","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1002\/eji.201646447","article-title":"Nonreversible MAIT cell-dysfunction in chronic hepatitis C virus infection despite successful interferon-free therapy","volume":"46","author":"Hengst","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Spaan, M., Hullegie, S.J., Beudeker, B.J., Kreefft, K., van Oord, G.W., Groothuismink, Z.M., van Tilborg, M., Rijnders, B., de Knegt, R.J., and Claassen, M.A. (2016). Frequencies of circulating MAIT cells are diminished in chronic HCV, HIV and HCV\/HIV co-infection and do not recover during therapy. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159243"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1053\/j.gastro.2017.07.043","article-title":"Intra-hepatic depletion of mucosal-associated invariant T cells in hepatitis C virus-induced liver inflammation","volume":"153","author":"Bolte","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.gendis.2015.01.001","article-title":"MicroRNAs: Role in hepatitis C virus pathogenesis","volume":"2","author":"Shrivastava","year":"2015","journal-title":"Genes Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6387","DOI":"10.1128\/JVI.00619-16","article-title":"HCV-induced up-regulation of miR-146a-5p in hepatocytes promotes viral infection and deregulates metabolic pathways associated with liver disease pathogenesis","volume":"90","author":"Bandiera","year":"2016","journal-title":"J. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.jhep.2014.10.004","article-title":"miR-122\u2014A key factor and therapeutic target in liver disease","volume":"62","author":"Bandiera","year":"2015","journal-title":"J. Hepatol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/10\/165\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:25:14Z","timestamp":1760196314000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/7\/10\/165"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,12]]},"references-count":81,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["cells7100165"],"URL":"https:\/\/doi.org\/10.3390\/cells7100165","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201810.0033.v1","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,12]]}}}