Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions
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 vira...
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Published in | Journal of general virology Vol. 95; no. 3; pp. 700 - 711 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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Society for General Microbiology
01.03.2014
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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. |
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AbstractList | 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. 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.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. 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. |
Author | Tarwater, Patrick Walker, Leah A. Murali, Ramachandran Hadi, Kevin Srinivasan, Alagarsamy Guha, Debjani Watkins, Simon C. Ayyavoo, Velpandi |
Author_xml | – sequence: 1 givenname: Kevin surname: Hadi fullname: Hadi, Kevin organization: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA – sequence: 2 givenname: Leah A. surname: Walker fullname: Walker, Leah A. organization: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA – sequence: 3 givenname: Debjani surname: Guha fullname: Guha, Debjani organization: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA – sequence: 4 givenname: Ramachandran surname: Murali fullname: Murali, Ramachandran organization: Department of Biomedical Sciences, Cedars–Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA, USA – sequence: 5 givenname: Simon C. surname: Watkins fullname: Watkins, Simon C. organization: Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA – sequence: 6 givenname: Patrick surname: Tarwater fullname: Tarwater, Patrick organization: Paul L. Foster School of Medicine, Texas Tech University Health Science Center, El Paso, TX, USA – sequence: 7 givenname: Alagarsamy surname: Srinivasan fullname: Srinivasan, Alagarsamy organization: NanoBio Diagnostics, West Chester, PA 19382, USA – sequence: 8 givenname: Velpandi surname: Ayyavoo fullname: Ayyavoo, Velpandi organization: Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261, USA |
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Snippet | Following infection with
Human immunodeficiency virus 1
(HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and... Following infection with Human immunodeficiency virus 1 (HIV-1) there is a remarkable variation in virus replication and disease progression. Both host and... |
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SubjectTerms | Animal Disease Progression G2 Phase Cell Cycle Checkpoints HIV Infections - pathology HIV Infections - physiopathology HIV Infections - virology HIV-1 - classification HIV-1 - genetics HIV-1 - isolation & purification HIV-1 - physiology Humans Phylogeny Polymorphism, Genetic Virus Replication vpr Gene Products, Human Immunodeficiency Virus - genetics vpr Gene Products, Human Immunodeficiency Virus - metabolism |
Title | Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions |
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