Nef enhances human immunodeficiency virus replication and responsiveness to interleukin-2 in human lymphoid tissue ex vivo
S Glushakova, JC Grivel, K Suryanarayana… - Journal of …, 1999 - Am Soc Microbiol
Journal of virology, 1999•Am Soc Microbiol
The nef gene is important for the pathogenicity associated with simian immunodeficiency
virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1)
infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo
remain unclear. We investigated the contribution of nef to HIV-1 replication in human
lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with a nef
mutant (Δ nef NL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than …
virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1)
infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo
remain unclear. We investigated the contribution of nef to HIV-1 replication in human
lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with a nef
mutant (Δ nef NL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than …
Abstract
The nef gene is important for the pathogenicity associated with simian immunodeficiency virus infection in rhesus monkeys and with human immunodeficiency virus type 1 (HIV-1) infection in humans. The mechanisms by which nef contributes to pathogenesis in vivo remain unclear. We investigated the contribution of nef to HIV-1 replication in human lymphoid tissue ex vivo by studying infection with parental HIV-1 strain NL4-3 and with anef mutant (ΔnefNL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than ΔnefNL4-3 did. Increased virus production with NL4-3 infection was associated with increased numbers of productively infected cells and greater loss of CD4+ T cells over time. While the numbers of productively infected T cells were increased in the presence of nef, the levels of viral expression and production per infected T cell were similar whether the nefgene was present or not. Exogenous interleukin-2 (IL-2) increased HIV-1 production in NL4-3-infected tissue in a dose-dependent manner. In contrast, ΔnefNL4-3 production was enhanced only marginally by IL-2. Thus, Nef can facilitate HIV-1 replication in human lymphoid tissue ex vivo by increasing the numbers of productively infected cells and by increasing the responsiveness to IL-2 stimulation.
American Society for Microbiology