Modelling the evolution and spread of HIV immune escape mutants

Fryer, Helen R, Frater, John, Duda, Anna, Roberts, Mick G, The SPARTAC Trial Investigators, , Phillips, Rodney E, McLean, Angela R and Fisher, Martin (2010) Modelling the evolution and spread of HIV immune escape mutants. PLoS Pathogens, 6 (11). e1001196. ISSN 1553-7366

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Abstract

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.

Item Type: Article
Additional Information: Martin Fisher is not a named author of this article but is one of the SPARTAC Trial investigators.
Schools and Departments: Brighton and Sussex Medical School > Brighton and Sussex Medical School
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine > RA0643 Communicable diseases and public health > RA0644 Individual diseases or groups of diseases, A-Z > RA0644.A25 AIDS. HIV infections
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Depositing User: Ellen Thomas
Date Deposited: 31 Mar 2014 14:28
Last Modified: 09 Mar 2017 06:26
URI: http://sro.sussex.ac.uk/id/eprint/47548

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