Vpr of simian immunodeficiency virus of African green monkeys is required for replication in macaque macrophages and lymphocytes

Abstract

The genomes of simian immunodeficiency viruses isolated from African green monkeys (SIVagm) contain a single accessory gene homolog of human immunodeficiency virus type 1 (HIV-1) vpr. This genomic organization differs from that of SIVsm-SIVmac-HIV-2 group viruses, which contain two gene homologs, designated vpr and vpx, which in combination appear to share the functions of HIV-1 vpr. The in vitro role of the SIVagm homolog was evaluated with molecularly cloned, pathogenic SIVagm9063-2. These studies revealed that this gene shares properties of HIV-1 vpr, such as nuclear and virion localization. In addition, SIVagm mutants with inactivating mutations of vpr are unable to replicate in nondividing cells, such as macaque monocyte-derived macrophages, but replicate to almost wild-type levels in a susceptible human T-cell line. The transport of virus preintegration complexes into the nucleus in primary macrophages, as measured by the production of unintegrated circular viral DNA, is less efficient for the mutant viruses than it is for the wild-type virus. SIVagm mutants also replicate inefficiently in primary macaque peripheral blood mononuclear cells, with a propensity for substitutions that remove the inserted inactivating stop codon. These data, in conjunction with recent findings that the Vpr protein is capable of inducing G2 arrest, are consistent with designation of this SIVagm accessory gene as vpr to reflect its shared functions and properties with HIV-1 vpr.