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Defining the roles for Vpr in HIV-1-associated neuropathogenesis
Journal article   Open access   Peer reviewed

Defining the roles for Vpr in HIV-1-associated neuropathogenesis

Tony James, Michael R Nonnemacher, Brian Wigdahl and Fred C Krebs
Journal of neurovirology, v 22(4), pp 403-415
Aug 2016
PMID: 27056720
url
https://doi.org/10.1007/s13365-016-0436-5View
Published, Version of Record (VoR) Open

Abstract

Neurons - pathology G2 Phase Cell Cycle Checkpoints - immunology Humans Central Nervous System - pathology Monocytes - immunology Central Nervous System - immunology T-Lymphocytes - virology Host-Pathogen Interactions - immunology HIV Infections - immunology HIV-1 - growth & development HIV Infections - pathology Monocytes - pathology Bystander Effect - genetics T-Lymphocytes - pathology Bystander Effect - immunology Central Nervous System - virology Neurons - virology Signal Transduction HIV Infections - genetics HIV Infections - virology Neurons - immunology vpr Gene Products, Human Immunodeficiency Virus - immunology HIV-1 - genetics Monocytes - virology G2 Phase Cell Cycle Checkpoints - genetics HIV-1 - immunology Virus Replication Gene Expression Regulation, Viral T-Lymphocytes - immunology vpr Gene Products, Human Immunodeficiency Virus - genetics
It is increasingly evident that the human immunodeficiency virus type 1 (HIV-1) 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 HIV-1 infection and replication in cells of monocytic origin (a key lineage of cells involved in HIV-1 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 HIV-1 sequence variation that results in functionally divergent Vpr variants; (ii) the dual activities of Vpr as a intracellular protein delivered and expressed during HIV-1 infection and as an extracellular protein that can act on neighboring, uninfected cells; (iii) cell type-dependent consequences of Vpr expression and exposure, including cell cycle arrest, metabolic dysregulation, and cytotoxicity; and (iv) the effects of Vpr on exosome-based intercellular communication in the CNS. Revealing that the effects of this pleiotropic viral protein is an essential part of a greater understanding of HIV-1-associated pathogenesis and potential approaches to treating and preventing disease caused by HIV-1 infection.

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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
Virology
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