Genome-wide analysis of primary peripheral blood mononuclear cells from HIV + patients-pre-and post- HAART show immune activation and inflammation the main drivers of host gene expression

  • Viviane Da Conceicao
  • Wayne Dyer
  • Kaushal Gandhi
  • Priyanka Gupta
  • Nitin Saksena
Keywords: Differentially Express, Differentially Express Gene, Plasma Viral Load, Host Gene Expression, Genomic Basis

Abstract

Although the host gene expression in the context of HIV has been explored by several studies, it remains unclear how HIV is able to manipulate and subvert host gene machinery before and after highly active antiretroviral therapy (HAART) in the same individual. In order to define the underlying pharmaco-genomic basis of HIV control during HAART and genomic basis of immune deterioration prior to HAART initiation, we performed a genome-wide expression analysis using primary peripheral blood mononuclear cells (PBMC) derived from 14 HIV + subjects pre-highly active antiretroviral therapy (HAART) (time point-1 or TP1) with detectable plasma viremia and post-HAART (time point-2 or TP2) with effective control of plasma viremia (<40 HIV RNA copies/mL of plasma).

Downloads

Download data is not yet available.

References

Cohen MS, Hellmann N, Levy JA, DeCock K, Lange J: The spread, treatment, and prevention of HIV-1: evolution of a global pandemic. J Clin Invest. 2008, 118 (4): 1244-1254. 10.1172/JCI34706.

PubMedCentralCrossRefPubMedGoogle Scholar

Cohen MS, Gay CL: Treatment to prevent transmission of HIV-1. Clin Infect Dis. 2010, 50 (Suppl 3): S85-95.

PubMedCentralCrossRefPubMedGoogle Scholar

Cao Y, Qin L, Zhang L, Safrit J, Ho DD: Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med. 1995, 332 (4): 201-208. 10.1056/NEJM199501263320401.

CrossRefPubMedGoogle Scholar

Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, Montefiori D, Orenstein JM, Fox C, Schrager LK, Margolick JB, Buchbinder S, Giorgi JV, Fauci AS: Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med. 1995, 332 (4): 209-216. 10.1056/NEJM199501263320402.

CrossRefPubMedGoogle Scholar

Paranjape RS: Immunopathogenesis of HIV infection. Indian J Med Res. 2005, 121 (4): 240-255.

PubMedGoogle Scholar

Wu JQ, Dwyer DE, Dyer WB, Yang YH, Wang B, Saksena NK: Transcriptional profiles in CD8+ T cells from HIV + progressors on HAART are characterized by coordinated up-regulation of oxidative phosphorylation enzymes and interferon responses. Virology. 2008, 380 (1): 124-135. 10.1016/j.virol.2008.06.039.

CrossRefPubMedGoogle Scholar

Wu JQ, Dwyer DE, Dyer WB, Yang YH, Wang B, Saksena NK: Genome-wide analysis of primary CD4+ and CD8+ T cell transcriptomes shows evidence for a network of enriched pathways associated with HIV disease. Retrovirology. 2011, 8: 18-10.1186/1742-4690-8-18.

PubMedCentralCrossRefPubMedGoogle Scholar

Wu JQ, Sasse TR, Wolkenstein G, Conceicao V, Saksena MM, Soedjono M, Perera SS, Wang B, Dwyer DE, Saksena NK: Transcriptome analysis of primary monocytes shows global down-regulation of genetic networks in HIV viremic patients versus long-term non-progressors. Virology. 2013, 435 (2): 308-319. 10.1016/j.virol.2012.10.026.

CrossRefPubMedGoogle Scholar

Van’t Wout AB, Lehrman GK, Mikheeva SA, O’Keefe GC, Katze MG, Bumgarner RE, Geiss GK, Mullins JI: Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4(+)-T-cell lines. J Virol. 2003, 77 (2): 1392-1402. 10.1128/JVI.77.2.1392-1402.2003.

CrossRefGoogle Scholar

Chan EY, Qian WJ, Diamond DL, Liu T, Gritsenko MA, Monroe ME, Camp DG, Smith RD, Katze MG: Quantitative analysis of human immunodeficiency virus type 1-infected CD4+ cell proteome: dysregulated cell cycle progression and nuclear transport coincide with robust virus production. J Virol. 2007, 81 (14): 7571-7583. 10.1128/JVI.00288-07.

PubMedCentralCrossRefPubMedGoogle Scholar

Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, Eron JJ, Feinberg JE, Balfour HH, Deyton LR, Chodakewitz JA, Fischl MA: A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997, 337 (11): 725-733. 10.1056/NEJM199709113371101.

CrossRefPubMedGoogle Scholar

Knapp WDB, Gilks W, Rieber EP, Schmidt RE, Stein H, von dem Borne AEGK: Leucocyte typing IV: white cell differentiation antigens. 1989, Oxford: Oxford University Press, 181-Volume 162

Google Scholar

Onate B, Vilahur G, Ferrer-Lorente R, Ybarra J, Diez-Caballero A, Ballesta-Lopez C, Moscatiello F, Herrero J, Badimon L: The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. FASEB J. 2012, 26 (10): 4327-4336. 10.1096/fj.12-207217.

CrossRefPubMedGoogle Scholar

Grabar S, Le Moing V, Goujard C, Leport C, Kazatchkine MD, Costagliola D, Weiss L: Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy. Ann Intern Med. 2000, 133 (6): 401-410. 10.7326/0003-4819-133-6-200009190-00007.

CrossRefPubMedGoogle Scholar

Li Q, Schacker T, Carlis J, Beilman G, Nguyen P, Haase AT: Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy. J Infect Dis. 2004, 189 (4): 572-582. 10.1086/381396.

CrossRefPubMedGoogle Scholar

Rotger M, Dang KK, Fellay J, Heinzen EL, Feng S, Descombes P, Shianna KV, Ge D, Gunthard HF, Goldstein DB, Telenti A: Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals. PLoS Pathog. 2010, 6 (2): e1000781-10.1371/journal.ppat.1000781.

PubMedCentralCrossRefPubMedGoogle Scholar

Howe EA, Sinha R, Schlauch D, Quackenbush J: RNA-Seq analysis in MeV. Bioinformatics. 2011, 27 (22): 3209-3210. 10.1093/bioinformatics/btr490.

PubMedCentralCrossRefPubMedGoogle Scholar

Butte A: The use and analysis of microarray data. Nat Rev Drug Discov. 2002, 1 (12): 951-960. 10.1038/nrd961.

CrossRefPubMedGoogle Scholar

Kato-Maeda M, Gao Q, Small PM: Microarray analysis of pathogens and their interaction with hosts. Cell Microbiol. 2001, 3 (11): 713-719. 10.1046/j.1462-5822.2001.00152.x.

CrossRefPubMedGoogle Scholar

Simon R, Lam A, Li MC, Ngan M, Menenzes S, Zhao Y: Analysis of gene expression data using BRB-ArrayTools. Cancer Inform. 2007, 3: 11-17.

PubMedCentralPubMedGoogle Scholar

Tusher VG, Tibshirani R, Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci U S A. 2001, 98 (9): 5116-5121. 10.1073/pnas.091062498.

PubMedCentralCrossRefPubMedGoogle Scholar

Gandhi KS, McKay FC, Cox M, Riveros C, Armstrong N, Heard RN, Vucic S, Wiliams DW, Stankovich J, Brown M, Danoy P, Stewart GJ, Broadley S, Moscato P, Lechner-Scott J, Scott RJ, Booth DR: The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis. Hum Mol Genet. 2010, 19 (11): 2134-2143. 10.1093/hmg/ddq090.

CrossRefPubMedGoogle Scholar

Giri MS, Nebozhyn M, Showe L, Montaner LJ: Microarray data on gene modulation by HIV-1 in immune cells: 2000-2006. J Leukoc Biol. 2006, 80 (5): 1031-1043.

CrossRefPubMedGoogle Scholar

Massanella M, Singhania A, Beliakova-Bethell N, Pier R, Lada SM, White CH, Perez-Santiago J, Blanco J, Richman DD, Little SJ, Woelk CH: Differential gene expression in HIV-infected individuals following ART. Antiviral Res. 2013, 100 (2): 420-428. 10.1016/j.antiviral.2013.07.017.

PubMedCentralCrossRefPubMedGoogle Scholar

Kaufmann GR, Perrin L, Pantaleo G, Opravil M, Furrer H, Telenti A, Hirschel B, Ledergerber B, Vernazza P, Bernasconi E, Rickenbach M, Egger M, Battegay M: CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med. 2003, 163 (18): 2187-2195. 10.1001/archinte.163.18.2187.

CrossRefPubMedGoogle Scholar

Benveniste O, Flahault A, Rollot F, Elbim C, Estaquier J, Pedron B, Duval X, Dereuddre-Bosquet N, Clayette P, Sterkers G, Simon A, Ameisen JC, Leport C: Mechanisms involved in the low-level regeneration of CD4+ cells in HIV-1-infected patients receiving highly active antiretroviral therapy who have prolonged undetectable plasma viral loads. J Infect Dis. 2005, 191 (10): 1670-1679. 10.1086/429670.

CrossRefPubMedGoogle Scholar

Emu B, Sinclair E, Favre D, Moretto WJ, Hsue P, Hoh R, Martin JN, Nixon DF, McCune JM, Deeks SG: Phenotypic, functional, and kinetic parameters associated with apparent T-cell control of human immunodeficiency virus replication in individuals with and without antiretroviral treatment. J Virol. 2005, 79 (22): 14169-14178. 10.1128/JVI.79.22.14169-14178.2005.

PubMedCentralCrossRefPubMedGoogle Scholar

Cossarini F, Boeri E, Canducci F, Salpietro S, Bigoloni A, Galli L, Spagnuolo V, Castagna A, Clementi M, Lazzarin A, Gianotti N: Integrase and fusion inhibitors transmitted drug resistance in naive patients with recent diagnosis of HIV-1 infection. J Acquir Immune Defic Syndr. 2011, 56 (2): e51-54. 10.1097/QAI.0b013e3181fcc0f1.

CrossRefPubMedGoogle Scholar

Kamga I, Kahi S, Develioglu L, Lichtner M, Maranon C, Deveau C, Meyer L, Goujard C, Lebon P, Sinet M, Hosmalin A: Type I interferon production is profoundly and transiently impaired in primary HIV-1 infection. J Infect Dis. 2005, 192 (2): 303-310. 10.1086/430931.

CrossRefPubMedGoogle Scholar

Shmelkov E, Tang Z, Aifantis I, Statnikov A: Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale. Biol Direct. 2011, 6: 15-10.1186/1745-6150-6-15.

PubMedCentralCrossRefPubMedGoogle Scholar

Brown JN, Kohler JJ, Coberley CR, Sleasman JW, Goodenow MM: HIV-1 activates macrophages independent of Toll-like receptors. PLoS One. 2008, 3 (12): e3664-10.1371/journal.pone.0003664.

PubMedCentralCrossRefPubMedGoogle Scholar

Barr SD, Smiley JR, Bushman FD: The interferon response inhibits HIV particle production by induction of TRIM22. PLoS Pathog. 2008, 4 (2): e1000007-10.1371/journal.ppat.1000007.

PubMedCentralCrossRefPubMedGoogle Scholar

Gougeon ML, Melki MT, Saidi H: HMGB1, an alarmin promoting HIV dissemination and latency in dendritic cells. Cell Death Differ. 2012, 19 (1): 96-106. 10.1038/cdd.2011.134.

PubMedCentralCrossRefPubMedGoogle Scholar

Li X, Jiang S, Tapping RI: Toll-like receptor signaling in cell proliferation and survival. Cytokine. 2010, 49 (1): 1-9. 10.1016/j.cyto.2009.08.010.

PubMedCentralCrossRefPubMedGoogle Scholar

Blasius AL, Beutler B: Intracellular toll-like receptors. Immunity. 2010, 32 (3): 305-315. 10.1016/j.immuni.2010.03.012.

CrossRefPubMedGoogle Scholar

Bowie AG, Haga IR: The role of Toll-like receptors in the host response to viruses. Mol Immunol. 2005, 42 (8): 859-867. 10.1016/j.molimm.2004.11.007.

CrossRefPubMedGoogle Scholar

Meier A, Alter G, Frahm N, Sidhu H, Li B, Bagchi A, Teigen N, Streeck H, Stellbrink HJ, Hellman J, van Lunzen J, Altfeld M: MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands. J Virol. 2007, 81 (15): 8180-8191. 10.1128/JVI.00421-07.

PubMedCentralCrossRefPubMedGoogle Scholar

Baenziger S, Heikenwalder M, Johansen P, Schlaepfer E, Hofer U, Miller RC, Diemand S, Honda K, Kundig TM, Aguzzi A, Speck RF: Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology. Blood. 2009, 113 (2): 377-388.

CrossRefPubMedGoogle Scholar

Mandl JN, Barry AP, Vanderford TH, Kozyr N, Chavan R, Klucking S, Barrat FJ, Coffman RL, Staprans SI, Feinberg MB: Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med. 2008, 14 (10): 1077-1087. 10.1038/nm.1871.

CrossRefPubMedGoogle Scholar

Published
2019-01-31
Section
Review