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Citations to this article

CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21
Huabiao Chen, … , Xu G. Yu, Mathias Lichterfeld
Huabiao Chen, … , Xu G. Yu, Mathias Lichterfeld
Published March 14, 2011
Citation Information: J Clin Invest. 2011;121(4):1549-1560. https://doi.org/10.1172/JCI44539.
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Research Article AIDS/HIV Article has an altmetric score of 8

CD4+ T cells from elite controllers resist HIV-1 infection by selective upregulation of p21

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Abstract

Elite controllers represent a unique group of HIV-1–infected persons with undetectable HIV-1 replication in the absence of antiretroviral therapy. However, the mechanisms contributing to effective viral immune defense in these patients remain unclear. Here, we show that compared with HIV-1 progressors and HIV-1–negative persons, CD4+ T cells from elite controllers are less susceptible to HIV-1 infection. This partial resistance to HIV-1 infection involved less effective reverse transcription and mRNA transcription from proviral DNA and was associated with strong and selective upregulation of the cyclin-dependent kinase inhibitor p21 (also known as cip-1 and waf-1). Experimental blockade of p21 in CD4+ T cells from elite controllers resulted in a marked increase of viral reverse transcripts and mRNA production and led to higher enzymatic activities of cyclin-dependent kinase 9 (CDK9), which serves as a transcriptional coactivator of HIV-1 gene expression. This suggests that p21 acts as a barrier against HIV-1 infection in CD4+ T cells from elite controllers by inhibiting a cyclin-dependent kinase required for effective HIV-1 replication. These data demonstrate a mechanism of host resistance to HIV-1 in elite controllers and may open novel perspectives for clinical strategies to prevent or treat HIV-1 infection.

Authors

Huabiao Chen, Chun Li, Jinghe Huang, Thai Cung, Katherine Seiss, Jill Beamon, Mary F. Carrington, Lindsay C. Porter, Patrick S. Burke, Yue Yang, Bethany J. Ryan, Ruiwu Liu, Robert H. Weiss, Florencia Pereyra, William D. Cress, Abraham L. Brass, Eric S. Rosenberg, Bruce D. Walker, Xu G. Yu, Mathias Lichterfeld

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Citations to this article (119)

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Expression profile of host restriction factors in HIV-1 elite controllers
M Abdel-Mohsen, RA Raposo, X Deng, M Li, T Liegler, E Sinclair, MS Salama, HE Ghanem, R Hoh, JK Wong, M David, DF Nixon, SG Deeks, SK Pillai
Retrovirology 2013
The natural history of HIV infection:
CA Sabin, JD Lundgren
Current Opinion in HIV and AIDS 2013
Long-Term Non-Progression and Broad HIV-1-Specific Proliferative T-Cell Responses
N Imami, SJ Westrop, N Grageda, AA Herasimtschuk
Frontiers in immunology 2013
A novel p21 attenuator which is structurally related to sorafenib
HI Wettersten, SH Hwang, C Li, EY Shiu, AT Wecksler, BD Hammock, RH Weiss
Cancer biology & therapy 2013
Lower HIV provirus levels are associated with more APOBEC3G protein in blood resting memory CD4+ T lymphocytes of controllers in vivo
MD Pasquale, Y Kourteva, T Allos, RT D'Aquila
PloS one 2013
Effects of cellular activation on anti-HIV-1 restriction factor expression profile in primary cells
RA Raposo, M Abdel-Mohsen, M Bilska, DC Montefiori, DF Nixon, SK Pillai
Journal of virology 2013
Lessons to be Learned from Natural Control of HIV - Future Directions, Therapeutic, and Preventive Implications
D Shasha, BD Walker
Frontiers in immunology 2013
The interplay between the X-DING-CD4, IFN-α and IL-8 gene activity in quiescent and mitogen- or HIV-1-exposed PBMCs from HIV-1 elite controllers, AIDS progressors and HIV-negative controls
R Sachdeva, RY Shilpi, M Simm
Innate immunity 2013
Cell-Mediated Immunity in Elite Controllers Naturally Controlling HIV Viral Load
L Genovese, M Nebuloni, M Alfano
Frontiers in immunology 2013
Impact of Protective KIR/HLA Genotypes on NK Cell and T Cell Function in HIV-1 Infected Controllers
C Tomescu, FM Duh, R Hoh, A Viviani, K Harvill, MP Martin, M Carrington, SG Deeks, LJ Montaner
AIDS 2012
Galectin-9 binding to Tim-3 renders activated human CD4+ T cells less susceptible to HIV-1 infection
S Elahi, T Niki, M Hirashima, H Horton
Blood 2012
The implications of viral reservoirs on the elite control of HIV-1 infection
RW Buckheit, M Salgado, KO Martins, JN Blankson
Cellular and Molecular Life Sciences 2012
Early HLA-B*57-restricted CD8+ T lymphocyte responses predict HIV-1 disease progression
CA Brennan, FJ Ibarrondo, CA Sugar, MA Hausner, R Shih, HL Ng, R Detels, JB Margolick, CR Rinaldo, J Phair, LP Jacobson, OO Yang, BD Jamieson
Journal of virology 2012
Thirty Years with HIV Infection—Nonprogression Is Still Puzzling: Lessons to Be Learned from Controllers and Long-Term Nonprogressors
JC Gaardbo, HJ Hartling, J Gerstoft, SD Nielsen
AIDS Research and Treatment 2012
Achieving a cure for HIV infection: do we have reasons to be optimistic?
VL Douce, A Janossy, H Hallay, S Ali, R Riclet, O Rohr, C Schwartz
Journal of Antimicrobial Chemotherapy 2012
Comprehensive analysis of unique cases with extraordinary control over HIV replication
D Mendoza, SA Johnson, BA Peterson, V Natarajan, M Salgado, RL Dewar, PD Burbelo, NA Doria-Rose, EH Graf, JH Greenwald, JN Hodge, WL Thompson, NA Cogliano, CL Chairez, CA Rehm, S Jones, CW Hallahan, JA Kovacs, I Sereti, O Sued, SA Peel, RJ O'Connell, U O'Doherty, TW Chun, M Connors, SA Migueles
Blood 2012
Elite controllers with low to absent effector CD8+ T cell responses maintain highly functional, broadly directed central memory responses
ZM Ndhlovu, J Proudfoot, K Cesa, DM Alvino, A McMullen, S Vine, E Stampouloglou, A Piechocka-Trocha, BD Walker, F Pereyra
Journal of virology 2012
Making a Short Story Long: Regulation of P-TEFb and HIV-1 Transcriptional Elongation in CD4+ T Lymphocytes and Macrophages
R Ramakrishnan, K Chiang, H Liu, S Budhiraja, H Donahue, AP Rice
Biology : open access journal 2012
Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy
M Salgado, SA Rabi, KA O'Connell, RW Buckheit, JR Bailey, AA Chaudhry, AR Breaud, MA Marzinke, W Clarke, JB Margolick, RF Siliciano, JN Blankson
Retrovirology 2011
HIV controllers: A multifactorial phenotype of spontaneous viral suppression
J Thèze, LA Chakrabarti, B Vingert, F Porichis, DE Kaufmann
Clinical Immunology 2011
A whole genome screen for HIV restriction factors
L Liu, NM Oliveira, KM Cheney, C Pade, H Dreja, AM Bergin, V Borgdorff, DH Beach, CL Bishop, MT Dittmar, A McKnight
Retrovirology 2011
Inhibition of HIV-1 Integration in Ex Vivo-Infected CD4 T Cells from Elite Controllers
MJ Buzon, K Seiss, R Weiss, AL Brass, ES Rosenberg, F Pereyra, XG Yu, M Lichterfeld
Journal of virology 2011
CD4+ T cells from elite suppressors are more susceptible to HIV-1 but produce fewer virions than cells from chronic progressors
KA O'Connell, SA Rabi, RF Siliciano, JN Blankson
Proceedings of the National Academy of Sciences 2011
The role of unintegrated DNA in HIV infection
RD Sloan, MA Wainberg
Retrovirology 2011
Elite control of HIV: p21 (waf-1/cip-1) at its best
XG Yu, M Lichterfeld
Cell cycle (Georgetown, Tex.) 2011
Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers
Sáez-Cirión A, Hamimi C, Bergamaschi A, David A, Versmisse P, Mélard A, Boufassa F, Barré-Sinoussi F, Lambotte O, Rouzioux C, Pancino G
Blood 2011
Pulmonary surfactant: an immunological perspective
ZC Chroneos, Z Sever-Chroneos, VL Shepherd
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2009

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