51. T cells from elite controllers resist HIV-1 infection by selective upregulation of p21
- Author
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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., and Lichterfeld, Mathias
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Gene expression -- Research ,T cells -- Research ,Disease susceptibility -- Research ,HIV infection -- Genetic aspects ,Health care industry - 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.sup.+] 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.sup.+] 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.sup.+] 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., Introduction HIV-1 infection leads to progressively rising viremia, loss of [CD4.sup.+] T cell counts, and clinical symptoms of immunodeficiency in the vast majority of untreated individuals; however, a small proportion [...]
- Published
- 2011
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