Defining the roles for Vpr in HIV-1-associated neuropathogenesis.
Tony JamesMichael R NonnemacherBrian WigdahlFred C KrebsPublished in: Journal of neurovirology (2016)
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.
Keyphrases
- antiretroviral therapy
- human immunodeficiency virus
- hiv infected
- cell cycle arrest
- hiv positive
- hiv aids
- hepatitis c virus
- induced apoptosis
- cell death
- hiv testing
- sars cov
- pi k akt
- protein protein
- men who have sex with men
- binding protein
- amino acid
- poor prognosis
- endoplasmic reticulum stress
- signaling pathway
- south africa
- copy number
- risk assessment
- long non coding rna
- oxidative stress
- gene expression
- cell proliferation
- genome wide