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

Bibliographic Collection: 
CARTA-Inspired Publication
Publication Type: Journal Article
Authors: Soto, PC; Karris, MY; Spina, CA; Richman, DD; Varki, A
Year of Publication: 2013
Journal: J Mol Med (Berl)
Volume: 91
Edition: 2012/09/05
Number: 2
Pagination: 261-70
Date Published: Feb
Type of Article: Research Support, American Recovery and Reinvestment ActResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.
Publication Language: eng
ISBN Number: 1432-1440 (Electronic)09
Accession Number: 22945238
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.

Notes:

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

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Author Address:

Department of Pathology, University of California, San Diego and Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.

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