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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1549-1560
Number of pages12
JournalJournal of Clinical Investigation
Volume121
Issue number4
DOIs
StatePublished - Apr 1 2011

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HIV Infections
HIV-1
Up-Regulation
T-Lymphocytes
Cyclin-Dependent Kinase 9
Cyclin-Dependent Kinase Inhibitor p21
Messenger RNA
Cyclin-Dependent Kinases
Reverse Transcription
Gene Expression
DNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chen, H., Li, C., Huang, J., Cung, T., Seiss, K., Beamon, J., ... Lichterfeld, M. (2011). CD4 + T cells from elite controllers resist HIV-1 infection by selective upregulation of p21. Journal of Clinical Investigation, 121(4), 1549-1560. https://doi.org/10.1172/JCI44539

CD4 + T cells from elite controllers resist HIV-1 infection by selective upregulation of p21. / Chen, Huabiao; Li, Chun; Huang, Jinghe; Cung, Thai; Seiss, Katherine; Beamon, Jill; Carrington, Mary F.; Porter, Lindsay C.; Burke, Patrick S.; Yang, Yue; Ryan, Bethany J.; Liu, Ruiwu; Weiss, Robert H; Pereyra, Florencia; Cress, William D.; Brass, Abraham L.; Rosenberg, Eric S.; Walker, Bruce D.; Yu, Xu G.; Lichterfeld, Mathias.

In: Journal of Clinical Investigation, Vol. 121, No. 4, 01.04.2011, p. 1549-1560.

Research output: Contribution to journalArticle

Chen, H, Li, C, Huang, J, Cung, T, Seiss, K, Beamon, J, Carrington, MF, Porter, LC, Burke, PS, Yang, Y, Ryan, BJ, Liu, R, Weiss, RH, Pereyra, F, Cress, WD, Brass, AL, Rosenberg, ES, Walker, BD, Yu, XG & Lichterfeld, M 2011, 'CD4 + T cells from elite controllers resist HIV-1 infection by selective upregulation of p21', Journal of Clinical Investigation, vol. 121, no. 4, pp. 1549-1560. https://doi.org/10.1172/JCI44539
Chen, Huabiao ; Li, Chun ; Huang, Jinghe ; Cung, Thai ; Seiss, Katherine ; Beamon, Jill ; Carrington, Mary F. ; Porter, Lindsay C. ; Burke, Patrick S. ; Yang, Yue ; Ryan, Bethany J. ; Liu, Ruiwu ; Weiss, Robert H ; Pereyra, Florencia ; Cress, William D. ; Brass, Abraham L. ; Rosenberg, Eric S. ; Walker, Bruce D. ; Yu, Xu G. ; Lichterfeld, Mathias. / CD4 + T cells from elite controllers resist HIV-1 infection by selective upregulation of p21. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 4. pp. 1549-1560.
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