title: Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status.
abstract: Even in the era of combination antiretroviral therapies used to combat human immunodeficiency virus type 1 (HIV-1) infection, up to 50 % of well-suppressed HIV-1-infected patients are still diagnosed with mild neurological deficits referred to as HIV-associated neurocognitive disorders (HAND). The multifactorial nature of HAND likely involves the HIV-1 accessory protein viral protein R (Vpr) as an agent of neuropathogenesis. To investigate the effect of naturally occurring variations in Vpr on HAND in well-suppressed HIV-1-infected patients, bioinformatic analyses were used to correlate peripheral blood-derived Vpr sequences with patient neurocognitive performance, as measured by comprehensive neuropsychological assessment and the resulting Global Deficit Score (GDS). Our studies revealed unique associations between GDS and the presence of specific amino acid changes in peripheral blood-derived Vpr sequences [neuropsychological impairment Vpr (niVpr) variants]. Amino acids N41 and A55 in the Vpr sequence were associated with more pronounced neurocognitive deficits (higher GDS). In contrast, amino acids I37 and S41 were connected to measurably lower GDS. All niVpr variants were also detected in DNA isolated from HIV-1-infected brain tissues. The implication of these results is that niVpr variants alter the genesis and/or progression of HAND through differences in Vpr-mediated effects in the peripheral blood and/or the brain.
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.|School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA.
authors.forename: Will
authors.initials: W
authors.lastname: Dampier
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.|School of Biomedical Engineering, Science, and Health Systems, Drexel University, Philadelphia, PA, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Antell
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Benjamas
authors.initials: B
authors.lastname: Aiamkitsumrit
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Nonnemacher
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Clinical and Translational Medicine, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.|Department of Medicine, Section of Infectious Disease, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Jacobson
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pirrone
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Kercher
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Shendra
authors.initials: S
authors.lastname: Passic
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Jean W
authors.initials: JW
authors.lastname: Williams
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: James
authors.affiliation: Department of Psychology, Temple University, Philadelphia, PA, USA.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: Devlin
authors.affiliation: Department of Psychology, Temple University, Philadelphia, PA, USA.
authors.forename: Tania
authors.initials: T
authors.lastname: Giovannetti
authors.affiliation: Department of Geriatrics and Gerontology, New Jersey Institute for Successful Aging, School of Osteopathic Medicine, Rowan University, Stratford, NJ, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Libon
authors.affiliation: Department of Medicine, Division of Infectious Diseases and HIV Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Szep
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Genomic Sciences, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Advanced Microbial Processing, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Garth D
authors.initials: GD
authors.lastname: Ehrlich
authors.affiliation: Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, USA.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, 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, Drexel University College of Medicine, Philadelphia, PA, USA. fred.krebs@drexelmed.edu.|Center for Molecular Virology and Translational Neuroscience, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Philadelphia, PA, USA. fred.krebs@drexelmed.edu.
authors.forename: Fred C
authors.initials: FC
authors.lastname: Krebs
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D001921:Brain / Q000473:pathology / Q000821:virology; D003071:Cognition / Q000502:physiology; D060825:Cognitive Dysfunction / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D015497:HIV-1; D054884:Host-Pathogen Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D054325:vpr Gene Products, Human Immunodeficiency Virus
keywords: GDS; HAND; HIV; Neuropathogenesis; Quasispecies; Sequence; Vpr