HIV-1 viral protein R (Vpr) & host cellular responses.
During infection of host cells by HIV-1, active host-pathogen interactions take place. The final balance between these interactions determines the efficiency of viral infection and subsequent disease progression. HIV-infected cells respond to viral invasion with various antiviral strategies such as innate, cellular and humoral immune antiviral defense mechanisms. On the other hand, the virus has also developed tactics to suppress these host cellular responses. Among the many viral offensive strategies, viral protein R (Vpr) plays a particularly active role. Vpr involved in nuclear transport of the viral pre-integration complex, activation of viral transcription, induction of cell cycle G2/M arrest and apoptosis of the host cells. However, specific roles of these Vpr activities in viral pathogenesis and their contribution to disease progression are not fully understood. HIV-1 defective for some or all of these Vpr activities have been associated with slow disease progression in some patients. With regard to the host responses to vpr gene expression, studies show that Vpr is specifically targeted by CD8 T-lymphocytes during acute viral infection and that the host innate immune response may also play a crucial role in suppressing the effects of Vpr on various cellular activities. The effect of host cellular responses to vpr gene expression and its roles in nuclear transport, cell cycle G2/M regulation and induction of apoptosis are discussed in this review. Strategies with potential application for future antiviral therapies directed at suppressing Vpr activities are described.
Zhao
Richard Yuqi
RY
Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, MSTF 600, Baltimore, MD 21201, USA. RZhao@som.maryland.edu
Bukrinsky
Michael
M
Elder
Robert T
RT
D017209:Apoptosis / Q000502:physiology; D002455:Cell Division; D018450:Disease Progression; D016195:G2 Phase; D016336:Gene Products, vpr / Q000502:physiology*; D006801:Humans; D007111:Immunity, Cellular
D016336:Gene Products, vpr