Modelling the Evolution and Spread of HIV Immune Escape Mutants

PLoS Pathogens

Mick G. Roberts¹  Helen R. Fryer²  Rodney E. Phillips²  John Frater³  Anna Duda³  The SPARTAC Trial Investigators³ 

[1] Institute of Information and Mathematical Sciences and New Zealand Institute for Advanced Study, Massey University, Auckland, New Zealand;The Institute for Emerging Infections, The James Martin 21st Century School, Department of Zoology, Oxford University, Oxford, United Kingdom;The Institute for Emerging Infections, The James Martin 21st Century School, The Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, Oxford University, Oxford, United Kingdom

关键词: HIV;    Viral evolution;    Evolutionary immunology;    Evolutionary rate;    Antimicrobial resistance;    Immune response;    Mathematical models;    Cohort studies;   

DOI  :  10.1371/journal.ppat.1001196

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

During infection with human immunodeficiency virus (HIV), immune pressure from cytotoxic T-lymphocytes (CTLs) selects for viral mutants that confer escape from CTL recognition. These escape variants can be transmitted between individuals where, depending upon their cost to viral fitness and the CTL responses made by the recipient, they may revert. The rates of within-host evolution and their concordant impact upon the rate of spread of escape mutants at the population level are uncertain. Here we present a mathematical model of within-host evolution of escape mutants, transmission of these variants between hosts and subsequent reversion in new hosts. The model is an extension of the well-known SI model of disease transmission and includes three further parameters that describe host immunogenetic heterogeneity and rates of within host viral evolution. We use the model to explain why some escape mutants appear to have stable prevalence whilst others are spreading through the population. Further, we use it to compare diverse datasets on CTL escape, highlighting where different sources agree or disagree on within-host evolutionary rates. The several dozen CTL epitopes we survey from HIV-1 gag, RT and nef reveal a relatively sedate rate of evolution with average rates of escape measured in years and reversion in decades. For many epitopes in HIV, occasional rapid within-host evolution is not reflected in fast evolution at the population level.

【 授权许可】

CC BY