title: Human immunodeficiency virus viral protein R as an extracellular protein in neuropathogenesis.
abstract: Numerous studies published in the past two decades have identified the viral protein R (Vpr) as one of the most versatile proteins in the life cycle of human immunodeficiency virus type 1 (HIV-1). In this regard, more than a thousand Vpr molecules are present in extracellular viral particles. Subsequent to viral entry, Vpr participates in early replicative events by assisting in viral genome nuclear import and, during the viral life cycle, by shuttling between the nucleus and the cytoplasm to accomplish its functions within the context of other replicative functions. Additionally, several studies have implicated Vpr as a proapoptotic protein because it promotes formation of permeability transition pores in mitochondria, which in turn affects transmembrane potential and adenosine triphosphate synthesis. Recent studies have identified Vpr as a virion-free protein in the serum and cerebrospinal fluid of patients infected with HIV-1 whose plasma viremia directly correlates with the extracellular concentration of Vpr. These observations pointed to a new role for Vpr as an additional weapon in the HIV-1 arsenal, involving the use of an extracellular protein to target and possibly inhibit HIV-1-uninfected bystander cells to enable them to escape immune surveillance. In addition, extracellular Vpr decreases adenosine triphosphate levels and affects the intracellular redox balance in neurons, ultimately causing their apoptosis. Herein, we review the role of Vpr as an extracellular protein and its downstream effects on cellular metabolism, functionality, and survival, with particular emphasis on how extracellular Vpr-induced oxidative stress might aggravate HIV-1-induced symptoms, thus affecting pathogenesis and disease progression.
authors.affiliation: School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, Pennsylvania, USA.
authors.forename: Adriano
authors.initials: A
authors.lastname: Ferrucci
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
mesh_terms: D017209:Apoptosis; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037521:Virulence Factors / Q000378:metabolism* / Q000633:toxicity; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000378:metabolism* / Q000633:toxicity
chemical_list: D037521:Virulence Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus
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