Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level
Corey B. Moore,1
Mina John,12
Ian R. James,1
Frank T. Christiansen,23
Campbell S. Witt,12
Simon A. Mallal12*
Antigen-specific T cell immunity is HLA-restricted.
Human immunodeficiency virus-type 1 (HIV-1) mutations that allow
escape from host immune responses may therefore be HLA
allele-specific. We analyzed HIV-1 reverse transcriptase sequences
from a large HLA-diverse population of HIV-1-infected individuals.
Polymorphisms in HIV-1 were most evident at sites of least
functional or structural constraint and frequently were associated with
particular host HLA class I alleles. Absence of polymorphism was also
HLA allele-specific. At a population level, the degree of
HLA-associated selection in viral sequence was predictive of viral
load. These results support a fundamental role for HLA-restricted
immune responses in driving and shaping HIV-1 evolution in vivo.
1 Centre for Clinical Immunology and Biomedical
Statistics, Royal Perth Hospital and Murdoch University, Level 2 North
Block, Royal Perth Hospital, Wellington Street, WA 6000, Australia.
2 Department of Clinical Immunology and Biochemical
Genetics, Royal Perth Hospital.
3 Department of
Pathology, University of Western Australia, WA 6009, Australia.
*
To whom correspondence should be addressed. E-mail:
mallal{at}prodigal.murdoch.edu.au
