Comparison of Cell Cycle Arrest, Transactivation, and Apoptosis Induced by the Simian Immunodeficiency Virus SIVagm and Human Immunodeficiency Virus Type 1vprGenes

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Abstract
All primate lentiviruses known to date contain one or two open reading frames with homology to the human immunodeficiency virus type 1 (HIV-1)vprgene. HIV-1vprencodes a 96-amino-acid protein with multiple functions in the viral life cycle. These functions include modulation of the viral replication kinetics, transactivation of the long terminal repeat, participation in the nuclear import of preintegration complexes, induction of G2arrest, and induction of apoptosis. The simian immunodeficiency virus (SIV) that infects African green monkeys (SIVagm) contains avprhomologue, which encodes a 118-amino-acid protein. SIVagmvpris structurally and functionally related to HIV-1vpr. The present study focuses on how three specific functions (transactivation, induction of G2arrest, and induction of apoptosis) are related to one another at a functional level, for HIV-1 and SIVagmvpr. While our study supports previous reports demonstrating a causal relationship between induction of G2arrest and transactivation for HIV-1vpr, we demonstrate that the same is not true for SIVagmvpr. Transactivation by SIVagmvpris independent of cell cycle perturbation. In addition, we show that induction of G2arrest is necessary for the induction of apoptosis by HIV-1vprbut that the induction of apoptosis by SIVagmvpris cell cycle independent. Finally, while SIVagmvprretains its transactivation function in human cells, it is unable to induce G2arrest or apoptosis in such cells, suggesting that the cytopathic effects of SIVagmvprare species specific. Taken together, our results suggest that while the multiple functions ofvprare conserved between HIV-1 and SIVagm, the mechanisms leading to the execution of such functions are divergent.