Project description:In contrast to SIVagm, which does not cause disease in its natural simian host, HIV-1 expresses the accessory protein Vpu and encodes a Nef protein that fails to suppress T cell activation via down-modulation of CD3. Although both, Vpu and Nef have been implicated as pathogenicity determinants, their relevance for viral replication and disease progression in vivo has remained unclear. Here, we analyzed gene expression in African green monkeys infected with SIVagm chimeras differing in their expression of nef and/or vpu. We used microarrays to analyze global gene expression of African green monkeys in response to infection with SIVagm and found that the viral accessory nef and vpu genes co-determine the induction of distinct gene sets. Overall design: Twelve juvenile female AGMs (Chlorocebus sabaeus) were randomly distributed to four groups with three monkeys each. The monkeys were infected with wild type SIVagm (WT; monkeys #14623, 14625, 14629), a chimera expressing SIVgsn Vpu (GU; #14624, 14627, 14632); a chimera expressing HIV-1 Nef (1N; #14626, 14630, 14631); or a double chimera expressing both SIVgsn Vpu and HIV-1 Nef (GU1N; #14628, 14633, 14634). RNA was isolated from whole blood 170 weeks post infection and whole genome microarray analysis was performed.