Chachage, M; Pollakis, G; Kuffour, EO; Haase, K; Bauer, A; Nadai, Y; Podola, L; ... Geldmacher, C; + view all Chachage, M; Pollakis, G; Kuffour, EO; Haase, K; Bauer, A; Nadai, Y; Podola, L; Clowes, P; Schiemann, M; Henkel, L; Hoffmann, D; Joseph, S; Bhuju, S; Maboko, L; Sarfo, FS; Eberhardt, K; Hoelscher, M; Feldt, T; Saathoff, E; Geldmacher, C; - view fewer (2016) CD25+FoxP3+ memory CD4 T cells are frequent targets of HIV infection in vivo. Journal of Virology , 90 (20) pp. 8954-8967. 10.1128/JVI.00612-16.

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Abstract

Interleukin 2 (IL2) signaling through the IL2 receptor alpha chain+ (CD25) facilitates HIV replication in vitro and facilitates homeostatic proliferation of CD25+FoxP3+CD4+ T cells. CD25+FoxP3+CD4+ T cells may therefore constitute a suitable subset for HIV infection and plasma virion production.CD25+FoxP3+CD4+ T cell frequencies, absolute numbers and the expression of CCR5 and cell cycle marker Ki67 were studied in peripheral blood from HIV+ and HIV- study volunteers. Different memory CD4+ T cell subsets were then sorted for quantification of cell-associated HIV-DNA and phylogenetic analyses of the highly variable EnvV1V3 region in comparison to plasma-derived virus sequences.In HIV+ subjects, 51% (median) of CD25+FoxP3+CD4+ T cells expressed the HIV co-receptor CCR5. Very high frequencies of Ki67+ cells were detected in CD25+FoxP3+ (median, 27.6%) in comparison to memory CD25-FoxP3- memory CD4+ T cells (median, 4.1%, p<0.0001). HIV-DNA content was 15-fold higher in CD25+FoxP3+ compared to CD25-FoxP3- memory CD4+ T cells (p=0.003). EnvV1V3 sequences derived from CD25+FoxP3+ memory CD4+ T cells did not preferentially cluster with plasma-derived sequences. Quasi-identical cell-plasma-sequence pairs were rare and their proportion further decreased with the estimated HIV infection duration.These data suggest that specific cellular characteristics of CD25+FoxP3+ memory CD4+ T cell might facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. Contribution of this cell population to plasma virion production remains unclear. IMPORTANCE: Despite recent advances in the understanding of AIDS virus pathogenesis, it is incompletely understood, which cell subsets support HIV infection and replication in vivo In vitro, the IL2 signaling pathway and IL2 dependent cell cycle induction are essential for HIV infection of stimulated T cells. CD25+FoxP3+ memory CD4 T cells - often referred to as regulatory CD4 T cells - depend on IL2 signaling for homeostatic proliferation in vivo Our results show that CD25+FoxP3+ memory CD4+ T cells often express the HIV co-receptor CCR5, are significantly more proliferative and contain more HIV-DNA compared to CD25-FoxP3- memory CD4 T cell subsets. The specific cellular characteristics of CD25+FoxP3+ memory CD4+ T cell probably facilitate efficient HIV infection in vivo and passage of HIV DNA to cell progeny in the absence of active viral replication. However contribution of this cell subset to plasma viremia remains unclear.

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