Human immunodeficiency virus type 1 Vpr polymorphisms associated with progressor and nonprogressor individuals alter Vpr-associated functions

Kevin Hadi, Leah A. Walker, Debjani Guha, Ramachandran Murali, Simon C. Watkins, Patrick Tarwater, Alagarsamy Srinivasan, Velpandi Ayyavoo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)700-711
Number of pages12
JournalJournal of General Virology
Volume95
Issue numberPART3
DOIs
StatePublished - Mar 2014
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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