Vpx is required for dissemination and pathogenesis of SIVSM PBj: Evidence of macrophage-dependent viral amplification

The viral accessory protein Vpx is required for productive in vitro infection of macrophages by simian immunodeficiency virus from sooty mangabey monkeys (SIV SM ). To evaluate the roles of Vpx and macrophage infection in vivo , we inoculated pigtailed macaques intravenously or intrarectally with the molecularly cloned, macrophage tropic, acutely pathogenic virus SIV SM PBj 6.6, or accessory gene deletion mutants (ΔVpr or ΔVpx) of this virus. Both wild-type and SIV SM PBj ΔVpx viruses were readily transmitted across the rectal mucosa. A subsequent 'stepwise' process of local amplification of infection and dissemination was observed for wild-type virus, but not for SIV SM PBj ΔVpx, which also showed considerable impairment of the overall kinetics and extent of its replication. In animals co-inoculated with equivalent amounts of wild-type and SIV SM Pbj ΔVpx intravenously or intrarectally, the ΔVpx mutant was at a strong competitive disadvantage. Vpx-dependent viral amplification at local sites of initial infection, perhaps through a macrophage-dependent mechanism, may be a prerequisite for efficient dissemination of infection and pathogenic consequences after exposure through either mucosal or intravenous routes.