PMID- 22674992
OWN - NLM
STAT- MEDLINE
DCOM- 20121010
LR  - 20220129
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 16
DP  - 2012 Aug
TI  - Cytotoxic T-lymphocyte escape mutations identified by HLA association favor those 
      which escape and revert rapidly.
PG  - 8568-80
LID - 10.1128/JVI.07020-11 [doi]
AB  - Identifying human immunodeficiency virus (HIV) immune escape mutations has 
      implications for understanding the impact of host immunity on pathogen evolution 
      and guiding the choice of vaccine antigens. One means of identifying 
      cytotoxic-T-lymphocyte (CTL) escape mutations is to search for statistical 
      associations between mutations and host human leukocyte antigen (HLA) class I 
      alleles at the population level. The impact of evolutionary rates on the strength 
      of such associations is not well defined. Here, we address this topic using a 
      mathematical model of within-host evolution and between-host transmission of CTL 
      escape mutants that predicts the prevalence of escape mutants at the population 
      level. We ask how the rates at which an escape mutation emerges in a host who 
      bears the restricting HLA and reverts when transmitted to a host who does not 
      bear the HLA affect the strength of an association. We consider the impact of 
      these factors when using a standard statistical method to test for an association 
      and when using an adaptation of that method that corrects for phylogenetic 
      relationships. We show that with both methods, the average sample size required 
      to identify an escape mutation is smaller if the mutation escapes and reverts 
      quickly. Thus, escape mutations identified as HLA associated systematically favor 
      those that escape and revert rapidly. We also present expressions that can be 
      used to infer escape and reversion rates from cross-sectional escape prevalence 
      data.
FAU - Fryer, Helen R
AU  - Fryer HR
AD  - The Institute for Emerging Infections, The Oxford Martin School, University of 
      Oxford, Oxford, United Kingdom. helen.fryer@zoo.ox.ac.uk
FAU - Frater, John
AU  - Frater J
FAU - Duda, Anna
AU  - Duda A
FAU - Palmer, Duncan
AU  - Palmer D
FAU - Phillips, Rodney E
AU  - Phillips RE
FAU - McLean, Angela R
AU  - McLean AR
LA  - eng
GR  - G108/626/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120606
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Epitopes, T-Lymphocyte/genetics/immunology
MH  - *Genes, MHC Class I
MH  - HIV/classification/*genetics/*immunology
MH  - HIV Infections/*immunology/transmission/*virology
MH  - Humans
MH  - Models, Theoretical
MH  - *Mutation
MH  - Phylogeny
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Viral Proteins/genetics/immunology
PMC - PMC3421756
EDAT- 2012/06/08 06:00
MHDA- 2012/10/12 06:00
PMCR- 2012/08/15
CRDT- 2012/06/08 06:00
PHST- 2012/06/08 06:00 [entrez]
PHST- 2012/06/08 06:00 [pubmed]
PHST- 2012/10/12 06:00 [medline]
PHST- 2012/08/15 00:00 [pmc-release]
AID - JVI.07020-11 [pii]
AID - 07020-11 [pii]
AID - 10.1128/JVI.07020-11 [doi]
PST - ppublish
SO  - J Virol. 2012 Aug;86(16):8568-80. doi: 10.1128/JVI.07020-11. Epub 2012 Jun 6.