The Decreased Replicative Capacity of Simian Immunodeficiency Virus SIVmac239ΔnefIs Manifest in Cultures of Immature Dendritic Cells and T Cells

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Abstract
Transmission of simian immunodeficiency virus SIVmac239Δnef(Δnef) 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 Δnefis 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 withnefdeleted (Δnef), irrespective of virus dose and the cell type introducing the virus to the coculture. In contrast, when immature DCs were exposed to Δnefand cocultured with T cells, virus replication was significantly lower than that of the wild type. Activation of the cultures with a superantigen allowed both Δnefand 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 Δnefin vitro and may contribute to the reduced pathogenicity of Δnefin vivo.