HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy

Journal of Virology

Volumn 88, Issue 6, 2014, Pages 3516-3526

  Murray, John M ^a,b   Zaunders, John J ^c   McBride, Kristin L ^b   Xu, Yin ^b   Bailey, Michelle ^b   Suzuki, Kazuo ^b   Cooper, David A ^b,c   Emery, Sean ^b   Kelleher, Anthony D ^b,c   Koelsch, Kersten K ^b  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b UNIVERSITY OF NEW SOUTH WALES   (Australia)

^c St Vincent's Centre for Applied Medical Research   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; CD38 ANTIGEN; HLA DR ANTIGEN; RALTEGRAVIR; VIRUS DNA; VIRUS RNA;

ARTICLE; CD4+ T LYMPHOCYTE; CONTROLLED STUDY; DRUG EFFECT; GENE FUNCTION; GENE IDENTIFICATION; HUMAN IMMUNODEFICIENCY VIRUS; LONG TERMINAL REPEAT; LYMPHOCYTE ACTIVATION; MEMORY T LYMPHOCYTE; MOLECULAR DYNAMICS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; VIRUS IDENTIFICATION; VIRUS LATENCY; VIRUS REPLICATION;

ANTI-HIV AGENTS; CD4-POSITIVE T-LYMPHOCYTES; COHORT STUDIES; DNA, VIRAL; HIV INFECTIONS; HIV-1; HUMANS; PYRROLIDINONES; VIRUS LATENCY;

EID: 84894554674     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.03331-13     Document Type: Article

References (44)

1. Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF. 1999. Latent infection of CD4+T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat. Med. 5:512-517. http://dx.doi.org/10.1038/8394.
2. + T cells while short ones are degraded. AIDS Res. Hum. Retroviruses 20:285-295. http://dx.doi.org/10.1089/088922204322996527.
3. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS. 1990. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61:213-222. http://dx.doi.org/10.1016/0092-8674(90)90802-L.
4. Swiggard WJ, Baytop C, Yu JJ, Dai J, Li C, Schretzenmair R, Theodosopoulos T, O'Doherty U. 2005. Human immunodeficiency virus type 1 can establish latent infection in resting CD4+ T cells in the absence of activating stimuli. J. Virol. 79:14179-14188. http://dx.doi.org/10.1128/JVI.79.22.14179-14188.2005.
5. Siliciano RF, Greene WC. 2011. HIV latency. Cold Spring Harb. Perspect. Med. 1:a007096. http://dx.doi.org/10.1101/cshperspect.a007096.
6. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel M-R, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy J-P, Haddad EK, Sekaly R-P. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15:893-900. http://dx.doi.org/10.1038/nm.1972.
7. Chun TW, Justement JS, Moir S, Hallahan CW, Maenza J, Mullins JI, Collier AC, Corey L, Fauci AS. 2007. Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: implications for eradication of virus. J. Infect. Dis. 195:1762-1764. http://dx.doi.org/10.1086/518250.
8. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF. 2003. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9:727-728. http://dx.doi.org/10.1038/nm880.
9. Koelsch KK, Boesecke C, McBride K, Gelgor L, Fahey P, Natarajan V, Baker D, Bloch M, Murray JM, Zaunders J, Emery S, Cooper DA, Kelleher AD, PINT Study Team. 2011. Impact of treatment with raltegravir during primary or chronic HIV infection on RNA decay characteristics and the HIV viral reservoir. AIDS 25:2069-2078. http://dx.doi.org/10.1097/QAD.0b013e32834b9658.
10. Murray JM, McBride K, Boesecke C, Bailey M, Amin J, Suzuki K, Baker D, Zaunders JJ, Emery S, Cooper DA, Koelsch KK, Kelleher AD. 2012. Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards. AIDS 26:543-550. http://dx.doi.org/10.1097/QAD.0b013e328350fb3c.
11. Brenchley JM, Hill BJ, Ambrozak DR, Price DA, Guenaga FJ, Casazza JP, Kuruppu J, Yazdani J, Migueles SA, Connors M, Roederer M, Douek DC, Koup RA. 2004. T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: implications for HIV pathogenesis. J. Virol. 78:1160-1168. http://dx.doi.org/10.1128/JVI.78.3.1160-1168.2004.
12. Zaunders JJ, Ip S, Munier ML, Kaufmann DE, Suzuki K, Brereton C, Sasson SC, Seddiki N, Koelsch K, Landay A, Grey P, Finlayson R, Kaldor J, Rosenberg ES, Walker BD, Fazekas de St. Groth B, Cooper DA, Kelleher AD. 2006. Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of CTLA-4 are linked to loss of antigenspecific CD4 T cells during primary human immunodeficiency virus type 1 infection. J. Virol. 80:10162-10172. http://dx.doi.org/10.1128/JVI.00249-06.
13. + T cells. AIDS Res. Hum. Retroviruses 29:1330-1339. http://dx.doi.org/10.1089/aid.2012.0351.
14. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. 2003. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J. Clin. Microbiol. 41:4531-4536. http://dx.doi.org/10.1128/JCM.41.10.4531-4536.2003.
15. Josefsson L, King MS, Makitalo B, Brännström J, Shao W, Maldarelli F, Kearney MF, Hu W-S, Chen J, Gaines H, Mellors JW, Albert J, Coffin JM, Palmer SE. 2011. Majority of CD4+ T cells from peripheral blood of HIV-1-infected individuals contain only one HIV DNA molecule. Proc. Natl. Acad. Sci. U.S.A. 108:11199-11204. http://dx.doi.org/10.1073/pnas.1107729108.
16. Koelsch KK, Liu L, Haubrich R, May S, Havlir D, Gunthard HF, Ignacio CC, Campos-Soto P, Little SJ, Shafer R, Robbins GK, D'Aquila RT, Kawano Y, Young K, Dao P, Spina CA, Richman DD, Wong JK. 2008. Dynamics of total, linear nonintegrated, and integrated HIV-1DNA in vivo and in vitro. J. Infect. Dis. 197:411-419. http://dx.doi.org/10.1086/525283.
17. Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. 1997. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387:188-191. http://dx.doi.org/10.1038/387188a0.
18. Sharkey ME, Teo I, Greenough T, Sharova N, Luzuriaga K, Sullivan JL, Bucy RP, Kostrikis LG, Haase A, Veryard C, Davaro RE, Cheeseman SH, Daly JS, Bova C, Ellison RT, III, Mady B, Lai KK, Moyle G, Nelson M, Gazzard B, Shaunak S, Stevenson M. 2000. Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nat. Med. 6:76-81. http://dx.doi.org/10.1038/71569.
19. Zaunders JJ, Cunningham PH, Kelleher AD, Kaufmann GR, Jaramillo AB, Wright R, Smith D, Grey P, Vizzard J, Carr A, Cooper DA. 1999. Potent antiretroviral therapy of primary human immunodeficiency virus type 1 (HIV-1) infection: partial normalization of T lymphocyte subsets and limited reduction of HIV-1 DNA despite clearance of plasma viremia. J. Infect. Dis. 180:320-329. http://dx.doi.org/10.1086/314880.
20. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M. 1995. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123-126. http://dx.doi.org/10.1038/373123a0.
21. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH. 1995. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117-122. http://dx.doi.org/10.1038/373117a0.
22. Meditz AL, Haas MK, Folkvord JM, Melander K, Young R, McCarter M, MaWhinney S, Campbell TB, Lie Y, Coakley E, Levy DN, Connick E. 2011. HLA-DR+ CD38+ CD4+ T lymphocytes have elevated CCR5 expression and produce the majority of R5-tropic HIV-1 RNA in vivo. J. Virol. 85:10189-10200. http://dx.doi.org/10.1128/JVI.02529-10.
23. Pierson TC, Zhou Y, Kieffer TL, Ruff CT, Buck C, Siliciano RF. 2002. Molecular characterization of preintegration latency in human immunodeficiency virus type 1 infection. J. Virol. 76:8518-8531. http://dx.doi.org/10.1128/JVI.76.17.8518-8513.2002.
24. Zhou Y, Zhang H, Siliciano JD, Siliciano RF. 2005. Kinetics of human immunodeficiency virus type 1 decay following entry into resting CD4+T cells. J. Virol. 79:2199-2210. http://dx.doi.org/10.1128/JVI.79.4.2199-2210.2005.
25. Mansharamani M, Graham DRM, Monie D, Lee KK, Hildreth JEK, Siliciano RF, Wilson KL. 2003. Barrier-to-autointegration factor BAF binds p55 Gag and matrix and is a host component of human immunodeficiency virus type 1 virions. J. Virol. 77:13084-13092. http://dx.doi.org/10.1128/JVI.77.24.13084-13092.2003.
26. Oswald-Richter K, Grill SM, Leelawong M, Unutmaz D. 2004. HIV infection of primary human T cells is determined by tunable thresholds of T cell activation. Eur. J. Immunol. 34:1705-1714. http://dx.doi.org/10.1002/eji.200424892.
27. Agosto LM, Yu JJ, Dai J, Kaletsky R, Monie D, O'Doherty U. 2007. HIV-1 integrates into resting CD4+ T cells even at low inoculums as demonstrated with an improved assay for HIV-1 integration. Virology 368:60-72. http://dx.doi.org/10.1016/j.virol.2007.06.001.
28. Pace MJ, Graf EH, Agosto LM, Mexas AM, Male F, Brady T, Bushman FD, O'Doherty U. 2012. Directly infected resting CD4+ T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 8:e1002818. http://dx.doi.org/10.1371/journal.ppat.1002 818.
29. Chun TW, Nickle DC, Justement JS, Large D, Semerjian A, Curlin ME, O'Shea MA, Hallahan CW, Daucher M, Ward DJ, Moir S, Mullins JI, Kovacs C, Fauci AS. 2005. HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J. Clin. Invest. 115:3250-3255. http://dx.doi.org/10.1172/JCI26197.
30. Levy Y, Sereti I, Tambussi G, Routy JP, Lelievre JD, Delfraissy JF, Molina JM, Fischl M, Goujard C, Rodriguez B, Rouzioux C, Avettand-Fenoel V, Croughs T, Beq S, Morre M, Poulin JF, Sekaly RP, Thiebaut R, Lederman MM. 2012. Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebocontrolled, multicenter study. Clin. Infect. Dis. 55:291-300. http://dx.doi.org/10.1093/cid/cis383.
31. Eriksson S, Graf EH, Dahl V, Strain MC, Yukl SA, Lysenko ES, Bosch RJ, Lai J, Chioma S, Emad F, Abdel-Mohsen M, Hoh R, Hecht F, Hunt P, Somsouk M, Wong J, Johnston R, Siliciano RF, Richman DD, O'Doherty U, Palmer S, Deeks SG, Siliciano JD. 2013. Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog. 9:e1003174. http://dx.doi.org/10.1371/journal.ppat.1003174.
32. Ho Y-C, Shan L, Hosmane NH, Wang J, Laskey SB, Rosenbloom DIS, Lai J, Blankson JN, Siliciano JD, Siliciano RF. 2013. Replicationcompetent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155:540-551. http://dx.doi.org/10.1016/j.cell.2013.09.020.
33. Mexas AM, Graf EH, Pace MJ, Yu JJ, Papasavvas E, Azzoni L, Busch MP, Di Mascio M, Foulkes AS, Migueles SA, Montaner LJ, O'Doherty U. 2012. Concurrent measures of total and integrated HIV DNA monitor reservoirs and ongoing replication in eradication trials. AIDS 26:2295-2306. http://dx.doi.org/10.1097/QAD.0b013e32835a5c2f.
34. Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, Brun SC, Kempf DJ, Mellors JW, Coffin JM, King MS. 2008. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc. Natl. Acad. Sci. U.S.A. 105:3879-3884. http://dx.doi.org/10.1073/pnas.0800050105.
35. Murray JM, Emery S, Kelleher AD, Law M, Chen J, Hazuda DJ, Nguyen BY, Teppler H, Cooper DA. 2007. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS 21:2315-2321.
36. Pace MJ, Graf EH, O'Doherty U. 2013. HIV 2-long terminal repeat circular DNA is stable in primary CD4+T cells. Virology 441:18-21. http://dx.doi.org/10.1016/j.virol.2013.02.028.
37. Pierson TC, Kieffer TL, Ruff CT, Buck C, Gange SJ, Siliciano RF. 2002. Intrinsic stability of episomal circles formed during human immunodeficiency virus type 1 replication. J. Virol. 76:4138-4144. http://dx.doi.org/10.1128/JVI.76.8.4138-4144.2002.
38. Sharkey M, Triques K, Kuritzkes DR, Stevenson M. 2005. In vivo evidence for instability of episomal human immunodeficiency virus type 1 cDNA. J. Virol. 79:5203-5210. http://dx.doi.org/10.1128/JVI.79.8.5203-5210.2005.
39. Ribeiro RM, Mohri H, Ho DD, Perelson AS. 2002. In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: why are CD4+ but not CD8+ T cells depleted? Proc. Natl. Acad. Sci. U.S.A. 99:15572-15577. http://dx.doi.org/10.1073/pnas.242358099.
40. Hazuda DJ, Felock P, Witmer M, Wolfe A, Stillmock K, Grobler JA, Espeseth A, Gabryelski L, Schleif W, Blau C, Miller MD. 2000. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 287:646-650. http://dx.doi.org/10.1126/science.287.5453.646.
41. Buzon M, Massanella M, Llibre JM, Esteve A, Dahl V, Puertas MC, Gatell JM, Domingo P, Paredes R, Sharkey M, Palmer S, Stevenson M, Clotet B, Blanco J, Martinez-Picado J. 2010. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAARTsuppressed subjects. Nat. Med. 16:460-465. http://dx.doi.org/10.1038/nm.2111.
42. Butler SL, Hansen MS, Bushman FD. 2001. A quantitative assay for HIV DNA integration in vivo. Nat. Med. 7:631-634. http://dx.doi.org/10.1038/87979.
43. Archin NM, Cheema M, Parker D, Wiegand A, Bosch RJ, Coffin JM, Eron J, Cohen M, Margolis DM. 2010. Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection. PLoS One 5:e9390. http://dx.doi.org/10.1371/journal.pone.0009390.
44. Blazkova J, Chun TW, Belay BW, Murray D, Justement JS, Funk EK, Nelson A, Hallahan CW, Moir S, Wender PA, Fauci AS. 2012. Effect of histone deacetylase inhibitors on HIV production in latently infected, resting CD4+T cells from infected individuals receiving effective antiretroviral therapy. J. Infect. Dis. 206:765-769. http://dx.doi.org/10.1093/infdis/jis412.