title: Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions.
abstract: Following infection with Human immunodeficiency virus 1 (HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and viral factors have been implicated in the observed differences in disease status. Here, we focus on understanding the contribution of HIV-1 viral protein R (Vpr) by evaluating the disease-associated Vpr polymorphism and its biological functions from HIV-1 positive rapid progressor (RP) and long-term nonprogressor (LTNP) subjects. Results presented here show distinct variation in phenotypes of Vpr alleles from LTNP and RP subjects. Most notably, the polymorphism of Vpr at R36W and L68M associated with RP shows higher levels of oligomerization, and increased virus replication, whereas R77Q exhibits poor replication kinetics. Interestingly, we did not observe correlation with cell cycle arrest function. Together these results indicate that polymorphisms in Vpr in part may contribute to altered virus replication kinetics leading to the observed differences in disease progression in LTNP and RP groups.
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hadi
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
authors.forename: Debjani
authors.initials: D
authors.lastname: Guha
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA.
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Murali
authors.affiliation: Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.affiliation: Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Tarwater
authors.affiliation: NanoBio Diagnostics, West Chester, PA 19382, USA.
authors.forename: Alagarsamy
authors.initials: A
authors.lastname: Srinivasan
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA.
authors.forename: Velpandi
authors.initials: V
authors.lastname: Ayyavoo
mesh_terms: D018450:Disease Progression; D059565:G2 Phase Cell Cycle Checkpoints; D015658:HIV Infections / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D010802:Phylogeny; D011110:Polymorphism, Genetic; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D054325:vpr Gene Products, Human Immunodeficiency Virus