Defining the roles for Vpr in HIV1associated neu

Authors: Tony James Michael R Nonnemacher Brian Wigdahl Fred C Krebs

Publish Date: 2016/04/07

Volume: 22, Issue: 4, Pages: 403-415

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Abstract

It is increasingly evident that the human immunodeficiency virus type 1 HIV1 viral protein R Vpr has a unique role in neuropathogenesis Its ability to induce G2/M arrest coupled with its capacity to increase viral gene transcription gives it a unique role in sustaining viral replication and aiding in the establishment and maintenance of a systemic infection The requirement of Vpr for HIV1 infection and replication in cells of monocytic origin a key lineage of cells involved in HIV1 neuroinvasion suggests an important role in establishing and sustaining infection in the central nervous system CNS Contributions of Vpr to neuropathogenesis can be expanded further through i naturally occurring HIV1 sequence variation that results in functionally divergent Vpr variants ii the dual activities of Vpr as a intracellular protein delivered and expressed during HIV1 infection and as an extracellular protein that can act on neighboring uninfected cells iii cell typedependent consequences of Vpr expression and exposure including cell cycle arrest metabolic dysregulation and cytotoxicity and iv the effects of Vpr on exosomebased intercellular communication in the CNS Revealing that the effects of this pleiotropic viral protein is an essential part of a greater understanding of HIV1associated pathogenesis and potential approaches to treating and preventing disease caused by HIV1 infectionThis work was partially supported by P30 MH092177 Comprehensive NeuroAIDS Center CNAC Program Director Kamel Khalili Brian Wigdahl PI of the Drexel subcontract These studies were also supported by the Public Health Service National Institutes of Health through grants from the National Institute of Neurological Disorders and Stroke NS32092 and NS46263 the National Institute of Drug Abuse DA19807 Dr Brian Wigdahl Principal Investigator and the National Institute of Mental Health under the Ruth L Kirschstein National Research Service Award 5T32MH079785 Jay Rappaport PI Brian Wigdahl PI of the Drexel subcontract The contents of the paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH Dr Michael Nonnemacher was supported in part by the Public Health Service National Institutes of Health through a grant from the National Institute of Neurological Disorders and Stroke NS089435 and faculty development funds provided by the Department of Microbiology and Immunology and the Institute for Molecular Medicine and Infectious Disease Dr Fred Krebs was supported by a developmental grant awarded by CNAC

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