Alex J. George Week 6

Env Gene Article
''Adaptation in the env Gene of HIV-1 and Evolutionary Theories of Disease Progression - S. Williamson

Introduction
 * HIV symptoms- after initial infection, long period of no symptoms follows during which CD4 T-cells decline
 * After the immune system can't contain viral replication, HIV progresses to AIDS
 * Many hypotheses suggest adaptation leads to pathogenicity
 * Characterizing rate and pattern of adaptation, removing misleading neutral mutations
 * "Env" gene codes for envelope glycoprotein gp160, which is precursor for gp41 and gp120
 * Focuses on region of "env" that gives rise to gp120--embedded in lipid membrane, responsible for host cell receptor binding site; divided into 5 regions (V1-V5)
 * Contains sites for antibodies, and two T lymphocytes

Results/Discussion
 * V1-V2 region has highest adaptation rates- once every 2.5 months- but are only from perinatally infected children
 * V3 region- one adaptive event per 5.9 months
 * V4-V5- every 12.2 months
 * Adaptive event occurs every 45 days in whole gene
 * Generation time of HIV-1: 1.2-2.6 days
 * Therefore, 1 adaptive event every 25 generations-- fastest rate in single protein-coding gene
 * Slow progressors= progression time to AIDS over 7 years; Moderate progressors= between 5-7 years
 * Adaptive events in slow progressors significantly higher than moderate
 * Viral adaptation in C2-V5 region is related to disease duration

Methods

 * We have run a multiple sequence alignment for Groups 1 and 2 separately to find the base pairs in which these subjects are similar
 * We then compared these same sequences between Groups 1 and 2 to find the base pair differences that are constant in Group 1 but are a different constant in Group 2


 * [[Media:HIV Presentation.ppt| HIV Research Presentation]]