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Waiting times for the appearance of cytotoxic T-lymphocyte escape mutants in chronic HIV-1 infection

Journal Article · · Virology
 [1];  [1];  [1]
  1. Department of Microbiology, University of Washington School of Medicine, Seattle, WA, 98195-8070 (United States)
The failure of HIV-1 to escape at some cytotoxic T-lymphocyte (CTL) epitopes has generally been explained in terms of viral fitness costs or ineffective or attenuated CTL responses. Relatively little attention has been paid to the evolutionary time required for escape mutants to be detected. This time is significantly affected by selection, mutation rates, the presence of other advantageous mutations, and the effective population size of HIV-1 in vivo (typically estimated to be {approx}10{sup 3} in chronically infected patients, though one study has estimated it to be {approx}10{sup 5}). Here, we use a forward simulator with experimentally estimated HIV-1 parameters to show that these delays can be substantial. For an effective population size of 10{sup 3}, even highly advantageous mutants (s = 0.5) may not be detected for a couple of years in chronically infected patients, while moderately advantageous escape mutants (s = 0.1) may not be detected for up to 10 years. Even with an effective population size of 10{sup 5}, a moderately advantageous escape mutant (s = 0.1) may not be detected in the population within 2 years if it has to compete with other selectively advantageous mutants. Stochastic evolutionary forces, therefore, in addition to viral fitness costs and ineffective or attenuated CTL responses, must be taken into account when assessing the selection of CTL escape mutations.
OSTI ID:
20779475
Journal Information:
Virology, Journal Name: Virology Journal Issue: 1 Vol. 347; ISSN VIRLAX; ISSN 0042-6822
Country of Publication:
United States
Language:
English

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