The decreased replicative capacity of SIVmac239delta nef is manifest in cultures of immature dendritic cells and T cells
Messmer,Davorka; Ignatius,Ralf; Santisteban,Christine; Steinman,Ralph M.; Pope,Melissa
Journal of Virology 74(5): 2406-2413
Publication date: 2000
Transmission of simian immunodeficiency virus SIVmac239nef (nef) to macaques results in attenuated replication of the virusin most animals and ultimately induces protection against challengewith some pathogenic, wild-type SIV strains. It has been difficult,however, to identify a culture system in which the replicationof nef is severely reduced relative to that of the wild type.We have utilized a primary culture system consisting of blood-deriveddendritic cells (DCs) and autologous T cells. When the DCs werefully differentiated or mature, the DC-CD4 T-cell mixtures supported replication of both the parental SIVstrain, 239 (the wild type), and its mutant with nef deleted (nef),irrespective of virus dose and the cell type introducing the virusto the coculture. In contrast, when immature DCs were exposedto nef and cocultured with T cells, virus replication was significantlylower than that of the wild type. Activation of the cultures witha superantigen allowed both nef and the wild type to replicatecomparably in immature DC-T-cell cultures. Immature DCs, which,it has been hypothesized, capture and transmit SIV in vivo, aredeficient in supporting replication of nef in vitro and may contributeto the reduced pathogenicity of nef invivo.