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 a
nef
mutant (Δ
nef
NL4-3). In human tonsillar histocultures, NL4-3 replicated to higher levels than Δ
nef
NL4-3 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
nef
gene 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, Δ
nef
NL4-3 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.
