Abstract
Transmission of simian immunodeficiency virus SIVmac239Delta(nef) (Delta(nef)) to macaques results in attenuated replication of the virus in most animals and ultimately induces protection against challenge with some pathogenic, wild-type SIV strains. It has been difficult, however, to identify a culture system in which the replication of Delta(nef) is severely reduced relative to that of the wild type. We have utilized a primary culture system consisting of blood-derived dendritic cells (DCs) and autologous T cells. When the DCs were fully differentiated or mature, the DC-CD4(+) T-cell mixtures supported replication of both the parental SIV strain, 239 (the wild type), and its mutant with nef deleted (Delta(nef)), irrespective of virus dose and the cell type introducing the virus to the coculture. In contrast, when immature DCs were exposed to Delta(nef) and cocultured with T cells, virus replication was significantly lower than that of the wild type. Activation of the cultures with a superantigen allowed both Delta(nef) and the wild type to replicate comparably in immature DC-T-cell cultures. Immature DCs, which, it has been hypothesized, capture and transmit SIV in vivo, are deficient in supporting replication of Delta(nef) in vitro and may contribute to the reduced pathogenicity of Delta(nef) in vivo.