In vitro replication of SIVcpz is suppressed by beta-chemokines and CD8+ T cells but not by natural killer cells of infected chimpanzees

Unlike humans, chimpanzees are relatively resistant to AIDS after infection with HIV-1 or simian immunodeficiency virus of chimpanzee (SIVcpz). We hypothesized that resistance to disease progression is associated with efficient suppression of virus replication possibly by beta-chemokines secreted by CD8+ lymphocytes and especially natural killer (NK) cells. In vitro suppression of virus replication can be easily studied in SIVcpz-infected chimpanzees because they produce high infectious virus titers in their peripheral blood. A study was undertaken to assess the sensitivity of SIVcpz to beta-chemokines in vitro and to investigate the role of endogenous beta-chemokines in relation to the in vitro capacity of CD8+ lymphocytes and NK cells of chimpanzees to suppress SIVcpz replication. Our results show that SIVcpz uses CCR5 as a coreceptor to gain cell entry and is sensitive to recombinant beta-chemokines in vitro. Here we report that despite their potent capacity to produce RANTES, NK cells of infected chimpanzees do not suppress SIVcpz replication in vitro, in contrast to CD8+ lymphocytes. We also show that endogenous beta-chemokines are not the predominant factors mediating in vitro suppression.