title: Cell-intrinsic mechanism involving Siglec-5 associated with divergent outcomes of HIV-1 infection in human and chimpanzee CD4 T cells.
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.
authors.affiliation: Department of Pathology, University of California, San Diego and Veterans Affairs San Diego Healthcare System, La Jolla, CA, USA.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Soto
authors.forename: Maile Y
authors.initials: MY
authors.lastname: Karris
authors.forename: Celsa A
authors.initials: CA
authors.lastname: Spina
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Richman
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D002679:Pan troglodytes
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D037102:Lectins; C114531:SIGLEC5 protein, human