Antiretroviral therapy for HIV and intrahepatic hepatitis C virus replication.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 03 2022
01 03 2022
Historique:
pubmed:
26
10
2021
medline:
9
4
2022
entrez:
25
10
2021
Statut:
ppublish
Résumé
HIV alters host responses to hepatitis C virus (HCV). However, the impact of antiretroviral therapy (ART) on HCV is rarely understood in relevant tissues and never before within individual hepatocytes. HIV and HCV kinetics were studied before and after ART initiation among 19 HIV/HCV co-infected persons. From five persons with the largest decline in plasma HCV RNA, liver tissues collected before and during ART, when plasma HIV RNA was undetectable, were studied. We used single-cell laser capture microdissection and quantitative PCR to assess intrahepatic HCV. Immunohistochemistry was performed to characterize intrahepatic immune cell populations. Plasma HCV RNA declined by 0.81 (0.52-1.60) log10 IU/ml from a median (range) 7.26 (6.05-7.29) log10 IU/ml and correlated with proportions of HCV-infected hepatocytes (r = 0.89, P = 2 × 10-5), which declined from median (range) of 37% (6-49%) to 23% (0.5-52%) after plasma HIV clearance. Median (range) HCV RNA abundance within cells was unchanged in four of five participants. Liver T-cell abundance unexpectedly decreased, whereas natural killer (NK) and NK T-cell infiltration increased, correlating with changes in proportions of HCV-infected hepatocytes (r = -0.82 and r = -0.73, respectively). Hepatocyte expression of HLA-E, an NK cell restriction marker, correlated with proportions of HCV-infected hepatocytes (r = 0.79). These are the first data to show that ART control of HIV reduces the intrahepatic burden of HCV. Furthermore, our data suggest that HIV affects the pathogenesis of HCV infection by an NK/NK T-cell-mediated mechanism that may involve HLA-E and can be rescued, at least in part, by ART.
Identifiants
pubmed: 34690280
doi: 10.1097/QAD.0000000000003116
pii: 00002030-202203010-00002
pmc: PMC9296270
mid: NIHMS1750370
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
337-346Subventions
Organisme : NIAID NIH HHS
ID : R01 AI116868
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI138810
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA013806
Pays : United States
Organisme : NIDA NIH HHS
ID : R37 DA013806
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Références
Foreman KJ, Marquez N, Dolgert A, Fukutaki K, Fullman N, McGaughey M, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories . Lancet 2018; 392:2052–2090.
Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC, et al. NA-ACCORD Investigators. Effect of early versus deferred antiretroviral therapy for HIV on survival . NEnglJ Med 2009; 360:1815–1826.
Smith CJ, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration . Lancet 2014; 384:241–248.
Eyawo O, Franco-Villalobos C, Hull MW, Nohpal A, Samji H, Sereda P, et al. Comparative Outcomes And Service Utilization Trends (COAST) study. Changes in mortality rates and causes of death in a population-based cohort of persons living with and without HIV from 1996 to 2012 . BMC Infect Dis 2017; 17:174.
Thomas DL, Astemborski J, Rai RM, Anania FA, Schaeffer M, Galai N, et al. The natural history of hepatitis C virus infection: host, viral, and environmental factors . JAMA 2000; 284:450–456.
Thomas DL, Shih JW, Alter HJ, Vlahov D, Cohn S, Hoover DR, et al. Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users . J Infect Dis 1996; 174:690–695.
Kirk GD, Mehta SH, Astemborski J, Galai N, Washington J, Higgins Y, et al. HIV, age, and the severity of hepatitis C virus-related liver disease: a cohort study . Ann Intern Med 2013; 158:658–666.
Qurishi N, Kreuzberg C, Luchters G, Effenberger W, Kupfer B, Sauerbruch T, et al. Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C coinfection . Lancet 2004; 362:1708–1713.
Kandathil AJ, Graw F, Quinn J, Hwang HS, Torbenson M, Perelson AS, et al. Use of laser capture microdissection to map HCV-positive hepatocytes in human liver . Gastroenterology 2013; 45:1404.e1–1413.e10.
Balagopal A, Kandathil AJ, Higgins YH, Wood J, Richer J, Quinn J, et al. Antiretroviral therapy, interferon sensitivity, and virologic setpoint in human immunodeficiency virus/hepatitis C virus coinfected patients . Hepatology 2014; 60:477–486.
El-Diwany R, Soliman M, Sugawara S, Breitwieser F, Skaist A, Coggiano C, et al. CMPK2 and BCL-G are associated with type 1 interferon-induced HIV restriction in humans . Sci Adv 2018; 4:eaat0843.
El-Diwany R, Breitwieser FP, Soliman M, Skaist AM, Srikrishna G, Blankson JN, et al. Intracellular HIV-1 rna and CD4+ t cell activation in patients starting antiretrovirals . AIDS 2017; 31:1405–1414.
Munshaw S, Bailey JR, Liu L, Osburn WO, Burke KP, Cox AL, Ray S. Computational reconstruction of bole1a, a representative synthetic hepatitis C virus subtype 1a genome . J Virol 2012; 86:5915–5921.
Wasilewski LN, El-Diwany R, Munshaw S, Snider AE, Brady JK, Osburn WO, et al. A hepatitis C virus envelope polymorphism confers resistance to neutralization by polyclonal sera and broadly neutralizing monoclonal antibodies . J Virol 2016; 90:3773–3782.
Sherman KE, Guedj J, Shata MT, Blackard JT, Rouster SD, Castro M, et al. Modulation of HCV replication after combination antiretroviral therapy in HCV/HIV co-infected patients . Sci Transl Med 2014; 6:246ra298.
Ramsuran V, Naranbhai V, Horowitz A, Qi Y, Martin MP, Yuki Y, et al. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells . Science 2018; 359:86–90.
Martin MP, Naranbhai V, Shea PR, Qi Y, Ramsuran V, Vince N, et al. Killer cell immunoglobulin-like receptor 3DL1 variation modifies HLA-B∗57 protection against HIV-1 . J Clin Invest 2018; 128:1903–1912.
Apps R, Qi Y, Carlson JM, Chen H, Gao X, Thomas R, et al. Influence of HLA-C expression level on HIV control . Science 2013; 340:87–91.
Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, et al. HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection . Science 2004; 305:872–874.
Thomas R, Thio CL, Apps R, Qi Y, Gao X, Marti D, et al. A novel variant marking HLA-DP expression levels predicts recovery from hepatitis B virus infection . JVirol 2012; 86:6979–6985.
van Stigt Thans T, Akko JI, Niehrs A, Garcia-Beltran WF, Richert L, Sturzel CM, et al. Primary HIV-1 strains use Nef to downmodulate HLA-E surface expression . J Virol 2019; 93:e00719-19.
Thoens C, Berger C, Trippler M, Siemann H, Lutterbeck M, Broering R, et al. KIR2DL3(+)NKG2A(−) natural killer cells are associated with protection from productive hepatitis C virus infection in people who inject drugs . J Hepatol 2014; 61:475–481.
Kaczmarek DJ, Kokordelis P, Kramer B, Glassner A, Wolter F, Goeser F, et al. Alterations of the NK cell pool in HIV/HCV co-infection . PLoS One 2017; 12:e0174465.
Goeser F, Glassner A, Kokordelis P, Wolter F, Lutz P, Kaczmarek DJ, et al. HIV mono-infection is associated with an impaired antihepatitis C virus activity of natural killer cells . AIDS 2016; 30:355–363.
Kokordelis P, Kramer B, Korner C, Boesecke C, Voigt E, Ingiliz P, et al. An effective interferon-gamma-mediated inhibition of hepatitis C virus replication by natural killer cells is associated with spontaneous clearance of acute hepatitis C in human immunodeficiency virus-positive patients . Hepatology 2014; 59:814–827.
Papasavvas E, Azzoni L, Yin X, Liu Q, Joseph J, Mackiewicz A, et al. HCV viraemia associates with NK cell activation and dysfunction in antiretroviral therapy-treated HIV/HCV-co-infected subjects . J Viral Hepat 2017; 24:865–876.
Zhang C, Wang XM, Li SR, Twelkmeyer T, Wang WH, Zhang SY, et al. NKG2A is a NK cell exhaustion checkpoint for HCV persistence . Nat Commun 2019; 10:1507.
Li F, Wei H, Wei H, Gao Y, Xu L, Yin W, et al. Blocking the natural killer cell inhibitory receptor NKG2A increases activity of human natural killer cells and clears hepatitis B virus infection in mice . Gastroenterology 2013; 144:392–401.
Korner C, Kramer B, Schulte D, Coenen M, Mauss S, Fatkenheuer G, et al. Effects of HCV co-infection on apoptosis of CD4+ T cells in HIV-positive patients . Clin Sci (Lond) 2009; 116:861–870.
Kandathil AJ, Sugawara S, Goyal A, Durand CM, Quinn J, Sachithanandham J, et al. No recovery of replication-competent HIV-1 from human liver macrophages . J Clin Invest 2018; 128:4501–4509.
Cao YZ, Dieterich D, Thomas PA, Huang YX, Mirabile M, Ho DD. Identification and quantitation of HIV-1 in the liver of patients with AIDS . AIDS 1992; 6:65–70.
Hufert FT, Schmitz J, Schreiber M, Schmitz H, Racz P, von Laer DD. Human Kupffer cells infected with HIV-1 in vivo . J Acquir Immune Defic Syndr (1988) 1993; 6:772–777.
Housset C, Boucher O, Girard PM, Leibowitch J, Saimot AG, Brechot C, et al. Immunohistochemical evidence for human immunodeficiency virus-1 infection of liver Kupffer cells . Hum Pathol 1990; 21:404–408.
Housset C, Lamas E, Brechot C. Detection of HIV1 RNA and p24 antigen in HIV1-infected human liver . ResVirol 1990; 141:153–159.
Kong L, Cardona Maya W, Moreno-Fernandez ME, Ma G, Shata MT, Sherman KE, et al. Low-level HIV infection of hepatocytes . Virol J 2012; 9:157.
Kong L, Welge JA, Powell EA, Blackard JT. HIV infection of hepatocytes results in a modest increase in hepatitis C virus expression in vitro . PLoS One 2014; 9:e83728.
Lin W, Tsai WL, Shao RX, Wu G, Peng LF, Barlow LL, et al. Hepatitis C virus regulates transforming growth factor beta1 production through the generation of reactive oxygen species in a nuclear factor kappaB-dependent manner . Gastroenterology 2010; 138:2509–2518. 2518.e1.
Salloum S, Holmes JA, Jindal R, Bale SS, Brisac C, Alatrakchi N, et al. Exposure to human immunodeficiency virus/hepatitis C virus in hepatic and stellate cell lines reveals cooperative profibrotic transcriptional activation between viruses and cell types . Hepatology 2016; 64:1951–1968.
Xiao P, Usami O, Suzuki Y, Ling H, Shimizu N, Hoshino H, et al. Characterization of a CD4-independent clinical HIV-1 that can efficiently infect human hepatocytes through chemokine (C-X-C motif) receptor 4 . AIDS 2008; 22:1749–1757.
Park IW, Fan Y, Luo X, Ryou MG, Liu J, Green L, He JJ. HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication . PLoS One 2014; 9:e99545.
Lin W, Weinberg EM, Tai AW, Peng LF, Brockman MA, Kim KA, et al. HIV increases HCV replication in a TGF-beta1-dependent manner . Gastroenterology 2008; 134:803–811.
Balagopal A, Ray SC, De Oca RM, Sutcliffe CG, Vivekanandan P, Higgins Y, et al. Kupffer cells are depleted with HIV immunodeficiency and partially recovered with antiretroviral immune reconstitution . AIDS 2009; 23:2397–2404.
Glas R, Franksson L, Une C, Eloranta ML, Ohlen C, Orn A, Kärre K. Recruitment and activation of natural killer (NK) cells in vivo determined by the target cell phenotype. An adaptive component of NK cell-mediated responses . J Exp Med 2000; 191:129–138.
Salazar-Mather TP, Orange JS, Biron CA. Early murine cytomegalovirus (MCMV) infection induces liver natural killer (NK) cell inflammation and protection through macrophage inflammatory protein 1alpha (MIP-1alpha)-dependent pathways . J Exp Med 1998; 187:1–14.
Natuk RJ, Welsh RM. Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication . J Immunol 1987; 138:877–883.
Chung RT, Evans SR, Yang Y, Theodore D, Valdez H, Clark R. AIDS Clinical Trials Group 383 Study Team. Immune recovery is associated with persistent rise in hepatitis C virus RNA, infrequent liver test flares, and is not impaired by hepatitis C virus in co-infected subjects . AIDS 2002; 16:1915–1923.
Ragni MV, Bontempo FA. Increase in hepatitis C virus load in hemophiliacs during treatment with highly active antiretroviral therapy . J InfectDis 1999; 180:2027–2029.