Defining the roles for Vpr in HIV-1-associated neuropathogenesis
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- 作者：Tony James ; Michael R. Nonnemacher ; Brian Wigdahl…
- 刊名：Journal of NeuroVirology
- 出版年：2016
- 出版时间：August 2016
- 年：2016
- 卷：22
- 期：4
- 页码：403-415
- 全文大小：1,190 KB
- 刊物主题：Neurosciences; Virology; Infectious Diseases; Immunology; Neurology;
- 出版者：Springer US
- ISSN：1538-2443
- 卷排序：22
文摘
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.KeywordsHIV-1VprNeuropathogenesisBrainExosome