Alex J. George Week 6

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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


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