HIV-1 Mediated Immune Pathogenesis: Spotlight on the Role of Viral Protein R (VPR)

Biswanath      Majumder; Narasimhan   J.   Venkatachari; Alagarsamy      Srinivasan; Velpandi      Ayyavoo

Abstract

HIV-1 exploits the cellular machinery to replicate in the host cells by targeting a wide range of host factors at different stages of its life cycle. HIV-1 also induces detrimental effects in the infected and uninfected bystander cells resulting in dysregulation including interference in immune effector functions. The latter is specifically linked to the immune evasion strategies of the virus. In addition to the essential roles of structural proteins (Gag, Pol & Env), HIV-1 encoded auxiliary proteins such as Nef, Vif, Vpu, and Vpr through their interaction with the host cellular partners facilitate viral replication and dissemination. HIV-1 Vpr, a virion-associated molecule, has been implicated to play a role in the early events in virus life cycle. Vpr is a pleiotropic protein that exerts a range of effects including inhibition of cell proliferation, induction of apoptosis and modulation of a number of immune molecules. These functions could be in part responsible for Vpr induced immune evasion and virus replication. Appreciating this view is the genetic variation in vpr gene reflected in the form of polymorphisms at the amino acid level that may contribute to the potential CTL escape of the virus. It is likely that Vpr mediated dysregulation of host immune response contributes, in part, to the progression of disease. This review focuses on the recent advances regarding HIV-1 Vpr mediated immunopathogenesis and the mechanistic insight from in vitro and in vivo studies.

Keywords: HIV-1 Vpr, immunopathogenesis, dendritic cells, T cells, NK cells, immune function

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