HIV-1 Accessory Protein Vpr: Relevance in the pathogenesis of HIV and potential for therapeutic intervention

Michael Kogan,Jay Rappaport

doi:10.1186/1742-4690-8-25

Abstract

The HIV protein, Vpr, is a multifunctional accessory protein critical for efficient viral infection of target CD4+ T cells and macrophages. Vpr is incorporated into virions and functions to transport the preintegration complex into the nucleus where the process of viral integration into the host genome is completed. This action is particularly important in macrophages, which as a result of their terminal differentiation and non-proliferative status, would be otherwise more refractory to HIV infection. Vpr has several other critical functions including activation of HIV-1 LTR transcription, cell-cycle arrest due to DCAF-1 binding, and both direct and indirect contributions to T-cell dysfunction. The interactions of Vpr with molecular pathways in the context of macrophages, on the other hand, support accumulation of a persistent reservoir of HIV infection in cells of the myeloid lineage. The role of Vpr in the virus life cycle, as well as its effects on immune cells, appears to play an important role in the immune pathogenesis of AIDS and the development of HIV induced end-organ disease. In view of the pivotal functions of Vpr in virus infection, replication, and persistence of infection, this protein represents an attractive target for therapeutic intervention.

Highlights

Human immunodeficiency virus type 1 (HIV-1) is a lentiviral family member that encodes retroviral Gag, Pol, and Env proteins along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Viral protein R (Vpr)
More than two decades of research on Vpr has greatly contributed to the knowledge scientists and clinicians have available about HIV-1 pathogenesis
The findings revealed that Vpr, while not essential for viral replication per se, is a biologically important, playing a critical role in the infection of non-dividing target cells including macrophages and resting T-cells

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) is a lentiviral family member that encodes retroviral Gag, Pol, and Env proteins along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. R80A mutant, as expected, showed no differences as compared to the other mutants in the number of G2 stage cells in terminally differentiated macrophages, as these cells are already arrested These results suggest that the so called G2 arrest property of Vpr is important in different ways than nuclear localization for productive viral infection in myeloid cells. The findings that demonstrate the importance of Vpr residues involved in G2 arrest in promoting HIV-1 replication likely suggest that the recruitment of native cellular factors to DCAF-1 promotes both properties It is unknown what binding partners mediate these effects or if they are the same or overlapping for both G2 arrest and cellular permissiveness. The consequences of Vpr on mitogenic transformation in vivo require further assessment and remain one potential limitation of such a therapeutic approach

Conclusion

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