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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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Total citations by year

Year: 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2009 Total
Citations: 2 5 11 1 8 10 8 8 9 12 10 17 9 8 1 119
Citation information
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Citations to this article in year 2014 (10)

Title and authors Publication Year
A Cell-Intrinsic Inhibitor of HIV-1 Reverse Transcription in CD4+ T Cells from Elite Controllers
J Leng, HP Ho, MJ Buzon, F Pereyra, BD Walker, XG Yu, EJ Chang, M Lichterfeld
Cell Host & Microbe 2014
Alteration of select gene expression patterns in individuals infected with HIV-1: Gene Expression Altered by HIV
E Serrao, CH Wang, T Frederick, CL Lee, P Anthony, D Arribas-Layton, K Baker, J Millstein, A Kovacs, N Neamati
Journal of Medical Virology 2014
Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?
A Saez-Cirion, B Jacquelin, F Barre-Sinoussi, M Muller-Trutwin
Philosophical Transactions of the Royal Society B: Biological Sciences 2014
Susceptibility to CD8 T-Cell–Mediated Killing Influences the Reservoir of Latently HIV-1–Infected CD4 T Cells:
MJ Buzon, Y Yang, Z Ouyang, H Sun, K Seiss, J Rogich, SL Gall, F Pereyra, ES Rosenberg, XG Yu, M Lichterfeld
Journal of acquired immune deficiency syndromes (1999) 2014
Efficient parvovirus replication requires CRL4Cdt2-targeted depletion of p21 to prevent its inhibitory interaction with PCNA
RO Adeyemi, MS Fuller, DJ Pintel
PLoS pathogens 2014
An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration
AD Olson, L Meyer, M Prins, R Thiebaut, D Gurdasani, M Guiguet, ML Chaix, P Amornkul, A Babiker, MS Sandhu, K Porter,
PloS one 2014
A correlate of HIV-1 control consisting of both innate and adaptive immune parameters best predicts viral load by multivariable analysis in HIV-1 infected viremic controllers and chronically-infected non-controllers
C Tomescu, Q Liu, BN Ross, X Yin, K Lynn, KC Mounzer, JR Kostman, LJ Montaner
PloS one 2014
TLR7 induces anergy in human CD4+ T cells
M Dominguez-Villar, AS Gautron, M Marcken, MJ Keller, DA Hafler
Nature Immunology 2014
SAMHD1 Specifically Affects the Antiviral Potency of Thymidine Analog HIV Reverse Transcriptase Inhibitors
E Ballana, R Badia, G Terradas, J Torres-Torronteras, A Ruiz, E Pauls, E Riveira-Munoz, B Clotet, R Marti, JA Este
Antimicrobial agents and chemotherapy 2014
Phenyl-1-Pyridin-2yl-Ethanone-Based Iron Chelators Increase I B-  Expression, Modulate CDK2 and CDK9 Activities, and Inhibit HIV-1 Transcription
N Kumari, S Iordanskiy, D Kovalskyy, D Breuer, X Niu, X Lin, M Xu, K Gavrilenko, F Kashanchi, S Dhawan, S Nekhai
Antimicrobial agents and chemotherapy 2014

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