TY  - UNPB
ID  - pittir13041
UR  - http://d-scholarship-dev.library.pitt.edu/13041/
A1  - Hadi, Kevin
Y1  - 2012/09/21/
N2  - Disease progression in individuals infected with human immunodeficiency virus type 1 (HIV-1) normally consists of a decline of the host immunity into acquired immunodeficiency syndrome (AIDS); this is a topic of great public health significance with the rapidly increasing prevalence of HIV-1 infected individuals. However 5% of the infected population resist AIDS development and remain asymptomatic. These so called long term non progressors (LTNPs) control the virus and are able to mount an effective immunological response. The role of the HIV accessory gene, Vpr, in differential disease progression is addressed in this study. For this purpose sequences identified from LTNPs and progressors (RP) from the HIV database from Los Alamos National Laboratories were analyzed to find signature polymorphisms in the amino acid sequence of this protein. Several mutations in the coding sequence of Vpr were found to be associated with the LTNPs, in particular, the threonine at position 19 mutated to alanine (T19A) and arginine at position 90 mutated to asparagine (R90N). In contrast the following mutations were found to be associated with RPs, arginine at position 36 mutated to tryptophan (R36W), leucine at position 68 mutated to methionine (L68M), and arginine at position 85 mutated to tyrosine (R85Y). A series of in vitro assays show that mainly the RP-associated mutations exhibit changes in several canonical functions of Vpr, namely, its capacity to oligomerize, localize to the nucleus, and induce G2 cell cycle arrest. However, infecting peripheral blood mononuclear cells (PBMCs) with viruses harboring these Vpr mutations demonstrates no difference in the replication capacity of the mutants compared to wild type virus. This study provides a basis to further delineate the mechanisms of Vpr function in disease progression.
KW  - HIV-1 Disease Progression LTNP Vpr Polymorphism Mutation
TI  - Disease Progression in HIV-1 and the Role of Polymorphisms in the VPR Gene
EP  - 101
AV  - public
ER  -