Cell-intrinsic mechanism involving Siglec-5 associated with divergent outcomes of HIV-1 infection in human and chimpanzee CD4 T cellsReport as inadecuate




Cell-intrinsic mechanism involving Siglec-5 associated with divergent outcomes of HIV-1 infection in human and chimpanzee CD4 T cells - Download this document for free, or read online. Document in PDF available to download.

Journal of Molecular Medicine

, Volume 91, Issue 2, pp 261–270

First Online: 04 September 2012Received: 29 May 2012Revised: 10 August 2012Accepted: 19 August 2012

Abstract

Human and chimpanzee CD4+ T cells differ markedly in expression of the inhibitory receptor Siglec-5, which contributes towards differential responses to activating stimuli. While CD4+ T cells from both species are equally susceptible to HIV-1 infection, chimpanzee cells survive better, suggesting a cell-intrinsic difference. We hypothesized that Siglec-5 expression protects T cells from activation-induced and HIV-1-induced cell death. Transduction of human CEM T cells with Siglec-5 decreased cell responses to stimulation. Following HIV-1 infection, a higher percentage of Siglec-5-positive cells survived, suggesting relative resistance to virus-induced cell death. Consistent with this, we observed an increase in percentage of Siglec-5-positive cells surviving in mixed infected cultures. Siglec-5-transduced cells also showed decreased expression of apoptosis-related proteins following infection and reduced susceptibility to Fas-mediated cell death. Similar Siglec-5-dependent differences were seen when comparing infection outcomes in primary CD4+ T cells from humans and chimpanzees. A protective effect of Siglec-5 was further supported by observing greater proportions of circulating CD4+ T cells expressing Siglec-5 in acutely infected HIV-1 patients, compared to controls. Taken together, our results suggest that Siglec-5 expression protects T cells from HIV-1- and apoptosis-induced cell death and contributes to the different outcomes of HIV-1 infection in humans and chimpanzees.

KeywordsHIV-1 infection CD4 Siglec-5  Download fulltext PDF



Author: Paula C. Soto - Maile Y. Karris - Celsa A. Spina - Douglas D. Richman - Ajit Varki

Source: https://link.springer.com/







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