@article {20323, title = {Cell-intrinsic mechanism involving Siglec-5 associated with divergent outcomes of HIV-1 infection in human and chimpanzee CD4 T cells}, journal = {J Mol Med (Berl)}, volume = {91}, number = {2}, year = {2013}, note = {

J Mol Med (Berl).\ 2013 Feb;91(2):261-70. doi: 10.1007/s00109-012-0951-7. Epub 2012 Sep 4.

}, month = {Feb}, pages = {261-70}, type = {Research Support, American Recovery and Reinvestment ActResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov{\textquoteright}tResearch Support, U.S. Gov{\textquoteright}t, Non-P.H.S.}, edition = {2012/09/05}, 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.

}, isbn = {1432-1440 (Electronic)09}, url = {http://www.ncbi.nlm.nih.gov/pubmed/22945238}, author = {Soto, PC and Karris, MY and Spina, CA and Richman, DD and Ajit Varki} }