title: Defining the roles for Vpr in HIV-1-associated neuropathogenesis.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Mail stop 1013-A, 245 N. 15th Street, Philadelphia, PA, 19102, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: James
authors.affiliation: Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Mail stop 1013-A, 245 N. 15th Street, Philadelphia, PA, 19102, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
authors.affiliation: Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Mail stop 1013-A, 245 N. 15th Street, Philadelphia, PA, 19102, USA.|Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Wigdahl
authors.affiliation: Department of Microbiology and Immunology, and Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Mail stop 1013-A, 245 N. 15th Street, Philadelphia, PA, 19102, USA. fred.krebs@drexelmed.edu.
authors.forename: Fred C
authors.identifier: 0000-0002-1530-4432
authors.initials: FC
authors.lastname: Krebs
mesh_terms: D024201:Bystander Effect / Q000235:genetics / Q000276:immunology; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology / Q000821:virology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D009474:Neurons / Q000276:immunology / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology
chemical_list: D054325:vpr Gene Products, Human Immunodeficiency Virus
keywords: Brain; Exosome; HIV-1; Neuropathogenesis; Vpr