HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Viral Stocks
2.3. Cellular Infection
2.4. Determination of HIV Latency Reversal
2.5. Statistical Analysis
3. Results
3.1. HIV-Infected Hepatic Stellate Cells (LX-2) Were Not Able to Reverse Viral Latency in J-Lat Cells
3.2. HCV-Infected Hepatocytes (Huh7.5 Cells) Were Not Able to Reverse Viral Latency in J-Lat Cells and U1 Cells
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- (WHO). W.H.O. Global HIV Programme. Available online: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/strategic-information/hiv-data-and-statistics (accessed on 29 July 2022).
- Back, D.; Marzolini, C. The challenge of HIV treatment in an era of polypharmacy. J. Int. AIDS Soc. 2020, 23, e25449. [Google Scholar] [CrossRef]
- Poorolajal, J.; Hooshmand, E.; Mahjub, H.; Esmailnasab, N.; Jenabi, E. Survival rate of AIDS disease and mortality in HIV-infected patients: A meta-analysis. Public Health 2016, 139, 3–12. [Google Scholar] [CrossRef] [PubMed]
- Barnighausen, T.; Bloom, D.E.; Humair, S. Human Resources for Treating HIV/AIDS: Are the Preventive Effects of Antiretroviral Treatment a Game Changer? PLoS ONE 2016, 11, e0163960. [Google Scholar] [CrossRef] [PubMed]
- Barton, K.M.; Palmer, S.E. How to Define the Latent Reservoir: Tools of the Trade. Curr. HIV/AIDS Rep. 2016, 13, 77–84. [Google Scholar] [CrossRef] [PubMed]
- Katlama, C.; Deeks, S.G.; Autran, B.; Martinez-Picado, J.; van Lunzen, J.; Rouzioux, C.; Miller, M.; Vella, S.; Schmitz, J.E.; Ahlers, J.; et al. Barriers to a cure for HIV: New ways to target and eradicate HIV-1 reservoirs. Lancet 2013, 381, 2109–2117. [Google Scholar] [CrossRef]
- Li, K.; Liu, B.; Ma, R.; Zhang, Q. HIV Tissue Reservoirs: Current Advances in Research. AIDS Patient Care STDs 2023, 37, 284–296. [Google Scholar] [CrossRef]
- Vanhamel, J.; Bruggemans, A.; Debyser, Z. Establishment of latent HIV-1 reservoirs: What do we really know? J. Virus Erad. 2019, 5, 3–9. [Google Scholar] [CrossRef] [PubMed]
- Dufour, C.; Gantner, P.; Fromentin, R.; Chomont, N. The multifaceted nature of HIV latency. J. Clin. Investig. 2020, 130, 3381–3390. [Google Scholar] [CrossRef]
- Wolf, G.; Singh, N.J. Modular Approaches to Understand the Immunobiology of Human Immunodeficiency Virus Latency. Viral Immunol. 2021, 34, 365–375. [Google Scholar] [CrossRef] [PubMed]
- Platt, L.; Easterbrook, P.; Gower, E.; McDonald, B.; Sabin, K.; McGowan, C.; Yanny, I.; Razavi, H.; Vickerman, P. Prevalence and burden of HCV co-infection in people living with HIV: A global systematic review and meta-analysis. Lancet. Infect. Dis. 2016, 16, 797–808. [Google Scholar] [CrossRef]
- Laskus, T.; Radkowski, M.; Piasek, A.; Nowicki, M.; Horban, A.; Cianciara, J.; Rakela, J. Hepatitis C virus in lymphoid cells of patients coinfected with human immunodeficiency virus type 1: Evidence of active replication in monocytes/macrophages and lymphocytes. J. Infect. Dis. 2000, 181, 442–448. [Google Scholar] [CrossRef] [PubMed]
- Blackard, J.T.; Smeaton, L.; Hiasa, Y.; Horiike, N.; Onji, M.; Jamieson, D.J.; Rodriguez, I.; Mayer, K.H.; Chung, R.T. Detection of hepatitis C virus (HCV) in serum and peripheral-blood mononuclear cells from HCV-monoinfected and HIV/HCV-coinfected persons. J. Infect. Dis. 2005, 192, 258–265. [Google Scholar] [CrossRef] [PubMed]
- Dobseu, R.; Nanfack, A.; Kowo, M.; Ambada, G.; Kamgaing, R.; Chenwi, C.; Fainguem, N.; Ka’e, A.; Ngangoum, E.; Sosso, S.; et al. Evaluation of hepatic fibrosis in HIV/HCV co-infected individuals in Yaounde, Cameroon: Usefulness of APRI score in resource-constrained settings. BMC Infect. Dis. 2020, 20, 758. [Google Scholar] [CrossRef] [PubMed]
- Joshi, D.; O’Grady, J.; Dieterich, D.; Gazzard, B.; Agarwal, K. Increasing burden of liver disease in patients with HIV infection. Lancet 2011, 377, 1198–1209. [Google Scholar] [CrossRef]
- Pembroke, T.; Deschenes, M.; Lebouche, B.; Benmassaoud, A.; Sewitch, M.; Ghali, P.; Wong, P.; Halme, A.; Vuille-Lessard, E.; Pexos, C.; et al. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis. J. Hepatol. 2017, 67, 801–808. [Google Scholar] [CrossRef]
- Darcis, G.; Bouchat, S.; Kula, A.; Van Driessche, B.; Delacourt, N.; Vanhulle, C.; Avettand-Fenoel, V.; De Wit, S.; Rohr, O.; Rouzioux, C.; et al. Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir. Aids 2017, 31, 181–189. [Google Scholar] [CrossRef]
- Nabel, G.; Baltimore, D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature 1987, 326, 711–713. [Google Scholar] [CrossRef] [PubMed]
- Stroud, J.C.; Oltman, A.; Han, A.; Bates, D.L.; Chen, L. Structural basis of HIV-1 activation by NF-kappaB—A higher-order complex of p50:RelA bound to the HIV-1 LTR. J. Mol. Biol. 2009, 393, 98–112. [Google Scholar] [CrossRef]
- Kushner, L.E.; Wendelboe, A.M.; Lazzeroni, L.C.; Chary, A.; Winters, M.A.; Osinusi, A.; Kottilil, S.; Polis, M.A.; Holodniy, M. Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients. PLoS ONE 2013, 8, e60387. [Google Scholar] [CrossRef] [PubMed]
- Marquez, M.; Romero-Cores, P.; Montes-Oca, M.; Martin-Aspas, A.; Soto-Cardenas, M.J.; Guerrero, F.; Fernandez-Gutierrez, C.; Giron-Gonzalez, J.A. Immune activation response in chronic HIV-infected patients: Influence of Hepatitis C virus coinfection. PLoS ONE 2015, 10, e0119568. [Google Scholar] [CrossRef]
- Lopez-Huertas, M.R.; Palladino, C.; Garrido-Arquero, M.; Esteban-Cartelle, B.; Sanchez-Carrillo, M.; Martinez-Roman, P.; Martin-Carbonero, L.; Ryan, P.; Dominguez-Dominguez, L.; Santos, I.L.; et al. HCV-coinfection is related to an increased HIV-1 reservoir size in cART-treated HIV patients: A cross-sectional study. Sci. Rep. 2019, 9, 5606. [Google Scholar] [CrossRef]
- Ganesan, M.; Poluektova, L.Y.; Kharbanda, K.K.; Osna, N.A. Liver as a target of human immunodeficiency virus infection. World J. Gastroenterol. 2018, 24, 4728–4737. [Google Scholar] [CrossRef]
- Chaillon, A.; Gianella, S.; Dellicour, S.; Rawlings, S.A.; Schlub, T.E.; De Oliveira, M.F.; Ignacio, C.; Porrachia, M.; Vrancken, B.; Smith, D.M. HIV persists throughout deep tissues with repopulation from multiple anatomical sources. J. Clin. Investig. 2020, 130, 1699–1712. [Google Scholar] [CrossRef] [PubMed]
- Jordan, A.; Bisgrove, D.; Verdin, E. HIV reproducibly establishes a latent infection after acute infection of T cells in vitro. EMBO J. 2003, 22, 1868–1877. [Google Scholar] [CrossRef] [PubMed]
- Bieniasz, P.D.; Cullen, B.R. Multiple blocks to human immunodeficiency virus type 1 replication in rodent cells. J. Virol. 2000, 74, 9868–9877. [Google Scholar] [CrossRef]
- Folks, T.M.; Justement, J.; Kinter, A.; Dinarello, C.A.; Fauci, A.S. Cytokine-induced expression of HIV-1 in a chronically infected promonocyte cell line. Science 1987, 238, 800–802. [Google Scholar] [CrossRef]
- Adachi, A.; Gendelman, H.E.; Koenig, S.; Folks, T.; Willey, R.; Rabson, A.; Martin, M.A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J. Virol. 1986, 59, 284–291. [Google Scholar] [CrossRef]
- Freed, E.O.; Englund, G.; Martin, M.A. Role of the basic domain of human immunodeficiency virus type 1 matrix in macrophage infection. J. Virol. 1995, 69, 3949–3954. [Google Scholar] [CrossRef] [PubMed]
- Mateu, G.; Donis, R.O.; Wakita, T.; Bukh, J.; Grakoui, A. Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death. Virology 2008, 376, 397–407. [Google Scholar] [CrossRef] [PubMed]
- Hokello, J.; Sharma, A.L.; Dimri, M.; Tyagi, M. Insights into the HIV Latency and the Role of Cytokines. Pathogens 2019, 8, 137. [Google Scholar] [CrossRef] [PubMed]
- Faulkner, N.E.; Lane, B.R.; Bock, P.J.; Markovitz, D.M. Protein phosphatase 2A enhances activation of human immunodeficiency virus type 1 by phorbol myristate acetate. J. Virol. 2003, 77, 2276–2281. [Google Scholar] [CrossRef] [PubMed]
- Poli, G.; Bressler, P.; Kinter, A.; Duh, E.; Timmer, W.C.; Rabson, A.; Justement, J.S.; Stanley, S.; Fauci, A.S. Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. J. Exp. Med. 1990, 172, 151–158. [Google Scholar] [CrossRef]
- Kruize, Z.; Kootstra, N.A. The Role of Macrophages in HIV-1 Persistence and Pathogenesis. Front. Microbiol. 2019, 10, 2828. [Google Scholar] [CrossRef]
- Mastroianni, C.M.; Lichtner, M.; Mascia, C.; Zuccala, P.; Vullo, V. Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. Int. J. Mol. Sci. 2014, 15, 9184–9208. [Google Scholar] [CrossRef] [PubMed]
- Lin, W.; Wu, G.; Li, S.; Weinberg, E.M.; Kumthip, K.; Peng, L.F.; Mendez-Navarro, J.; Chen, W.C.; Jilg, N.; Zhao, H.; et al. HIV and HCV cooperatively promote hepatic fibrogenesis via induction of reactive oxygen species and NFkappaB. J. Biol. Chem. 2011, 286, 2665–2674. [Google Scholar] [CrossRef]
- Semmo, N.; Klenerman, P. CD4+ T cell responses in hepatitis C virus infection. World J. Gastroenterol. 2007, 13, 4831–4838. [Google Scholar] [CrossRef]
- Gao, B.; Jeong, W.I.; Tian, Z. Liver: An organ with predominant innate immunity. Hepatology 2008, 47, 729–736. [Google Scholar] [CrossRef] [PubMed]
- Szabo, G.; Mandrekar, P.; Dolganiuc, A. Innate immune response and hepatic inflammation. Semin. Liver Dis. 2007, 27, 339–350. [Google Scholar] [CrossRef] [PubMed]
- Presser, L.D.; Haskett, A.; Waris, G. Hepatitis C virus-induced furin and thrombospondin-1 activate TGF-beta1: Role of TGF-beta1 in HCV replication. Virology 2011, 412, 284–296. [Google Scholar] [CrossRef] [PubMed]
- Taniguchi, H.; Kato, N.; Otsuka, M.; Goto, T.; Yoshida, H.; Shiratori, Y.; Omata, M. Hepatitis C virus core protein upregulates transforming growth factor-beta 1 transcription. J. Med. Virol. 2004, 72, 52–59. [Google Scholar] [CrossRef] [PubMed]
- Sandler, N.G.; Koh, C.; Roque, A.; Eccleston, J.L.; Siegel, R.B.; Demino, M.; Kleiner, D.E.; Deeks, S.G.; Liang, T.J.; Heller, T.; et al. Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection. Gastroenterology 2011, 141, 1220–1230, 1230 e1221–1223. [Google Scholar] [CrossRef] [PubMed]
- Gobran, S.T.; Ancuta, P.; Shoukry, N.H. A Tale of Two Viruses: Immunological Insights Into HCV/HIV Coinfection. Front. Immunol. 2021, 12, 726419. [Google Scholar] [CrossRef]
- Margolis, D.M.; Archin, N.M.; Cohen, M.S.; Eron, J.J.; Ferrari, G.; Garcia, J.V.; Gay, C.L.; Goonetilleke, N.; Joseph, S.B.; Swanstrom, R.; et al. Curing HIV: Seeking to Target and Clear Persistent Infection. Cell 2020, 181, 189–206. [Google Scholar] [CrossRef]
- Wen, Y.; Lambrecht, J.; Ju, C.; Tacke, F. Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities. Cell Mol. Immunol. 2021, 18, 45–56. [Google Scholar] [CrossRef]
- Ficht, X.; Iannacone, M. Immune surveillance of the liver by T cells. Sci. Immunol. 2020, 5, eaba2351. [Google Scholar] [CrossRef]
- Friedman, S.L. Mechanisms of hepatic fibrogenesis. Gastroenterology 2008, 134, 1655–1669. [Google Scholar] [CrossRef]
- Chen, W.; Xu, Y.; Li, H.; Tao, W.; Xiang, Y.; Huang, B.; Niu, J.; Zhong, J.; Meng, G. HCV genomic RNA activates the NLRP3 inflammasome in human myeloid cells. PLoS ONE 2014, 9, e84953. [Google Scholar] [CrossRef] [PubMed]
- Salloum, S.; Holmes, J.A.; Jindal, R.; Bale, S.S.; Brisac, C.; Alatrakchi, N.; Lidofsky, A.; Kruger, A.J.; Fusco, D.N.; Luther, J.; 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. [Google Scholar] [CrossRef] [PubMed]
- Rezaei, S.D.; Lu, H.K.; Chang, J.J.; Rhodes, A.; Lewin, S.R.; Cameron, P.U. The Pathway To Establishing HIV Latency Is Critical to How Latency Is Maintained and Reversed. J. Virol. 2018, 92, 10–1128. [Google Scholar] [CrossRef]
- Kandathil, A.J.; Sugawara, S.; Goyal, A.; Durand, C.M.; Quinn, J.; Sachithanandham, J.; Cameron, A.M.; Bailey, J.R.; Perelson, A.S.; Balagopal, A. No recovery of replication-competent HIV-1 from human liver macrophages. J. Clin. Investig. 2018, 128, 4501–4509. [Google Scholar] [CrossRef] [PubMed]
- Crispe, I.N. Immune tolerance in liver disease. Hepatology 2014, 60, 2109–2117. [Google Scholar] [CrossRef]
- Cao, Y.Z.; Dieterich, D.; Thomas, P.A.; Huang, Y.X.; Mirabile, M.; Ho, D.D. Identification and quantitation of HIV-1 in the liver of patients with AIDS. Aids 1992, 6, 65–70. [Google Scholar] [CrossRef] [PubMed]
- Veenhuis, R.T.; Abreu, C.M.; Costa, P.A.G.; Ferreira, E.A.; Ratliff, J.; Pohlenz, L.; Shirk, E.N.; Rubin, L.H.; Blankson, J.N.; Gama, L.; et al. Monocyte-derived macrophages contain persistent latent HIV reservoirs. Nat. Microbiol. 2023, 8, 833–844. [Google Scholar] [CrossRef] [PubMed]
- Fulcher, J.A.; Hwangbo, Y.; Zioni, R.; Nickle, D.; Lin, X.; Heath, L.; Mullins, J.I.; Corey, L.; Zhu, T. Compartmentalization of human immunodeficiency virus type 1 between blood monocytes and CD4+ T cells during infection. J. Virol. 2004, 78, 7883–7893. [Google Scholar] [CrossRef] [PubMed]
- Lee, B.; Sharron, M.; Montaner, L.J.; Weissman, D.; Doms, R.W. Quantification of CD4, CCR5, and CXCR4 levels on lymphocyte subsets, dendritic cells, and differentially conditioned monocyte-derived macrophages. Proc. Natl. Acad. Sci. USA 1999, 96, 5215–5220. [Google Scholar] [CrossRef]
- Koppensteiner, H.; Brack-Werner, R.; Schindler, M. Macrophages and their relevance in Human Immunodeficiency Virus Type I infection. Retrovirology 2012, 9, 82. [Google Scholar] [CrossRef] [PubMed]
- Sattentau, Q.J.; Stevenson, M. Macrophages and HIV-1: An Unhealthy Constellation. Cell Host Microbe 2016, 19, 304–310. [Google Scholar] [CrossRef]
- Crowe, S.; Zhu, T.; Muller, W.A. The contribution of monocyte infection and trafficking to viral persistence, and maintenance of the viral reservoir in HIV infection. J. Leukoc. Biol. 2003, 74, 635–641. [Google Scholar] [CrossRef]
- Chandra, P.K.; Gerlach, S.L.; Wu, C.; Khurana, N.; Swientoniewski, L.T.; Abdel-Mageed, A.B.; Li, J.; Braun, S.E.; Mondal, D. Mesenchymal stem cells are attracted to latent HIV-1-infected cells and enable virus reactivation via a non-canonical PI3K-NFkappaB signaling pathway. Sci. Rep. 2018, 8, 14702. [Google Scholar] [CrossRef]
- Pallikkuth, S.; Mohan, M. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication. Trends Microbiol. 2015, 23, 748–750. [Google Scholar] [CrossRef]
- Pallikkuth, S.; Sharkey, M.; Babic, D.Z.; Gupta, S.; Stone, G.W.; Fischl, M.A.; Stevenson, M.; Pahwa, S. Peripheral T Follicular Helper Cells Are the Major HIV Reservoir within Central Memory CD4 T Cells in Peripheral Blood from Chronically HIV-Infected Individuals on Combination Antiretroviral Therapy. J. Virol. 2015, 90, 2718–2728. [Google Scholar] [CrossRef] [PubMed]
- Fuller, K.; Owens, J.M.; Jagger, C.J.; Wilson, A.; Moss, R.; Chambers, T.J. Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts. J. Exp. Med. 1993, 178, 1733–1744. [Google Scholar] [CrossRef] [PubMed]
- Rasmussen, T.A.; Lewin, S.R. Shocking HIV out of hiding: Where are we with clinical trials of latency reversing agents? Curr. Opin. HIV AIDS 2016, 11, 394–401. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
López, C.A.M.; Freiberger, R.N.; Sviercz, F.A.; Quarleri, J.; Delpino, M.V. HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells. Pathogens 2024, 13, 134. https://doi.org/10.3390/pathogens13020134
López CAM, Freiberger RN, Sviercz FA, Quarleri J, Delpino MV. HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells. Pathogens. 2024; 13(2):134. https://doi.org/10.3390/pathogens13020134
Chicago/Turabian StyleLópez, Cinthya Alicia Marcela, Rosa Nicole Freiberger, Franco Agustín Sviercz, Jorge Quarleri, and María Victoria Delpino. 2024. "HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells" Pathogens 13, no. 2: 134. https://doi.org/10.3390/pathogens13020134
APA StyleLópez, C. A. M., Freiberger, R. N., Sviercz, F. A., Quarleri, J., & Delpino, M. V. (2024). HIV-Infected Hepatic Stellate Cells or HCV-Infected Hepatocytes Are Unable to Promote Latency Reversal among HIV-Infected Mononuclear Cells. Pathogens, 13(2), 134. https://doi.org/10.3390/pathogens13020134