Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Koch:2017:molbev/msx107,
author = {Koch, AS and Brites, D and Stucki, D and Evans, JC and Seldon, R and Heekes, A and Mulder, N and Nicol, M and Oni, T and Mizrahi, V and Warner, DF and Parkhill, J and Gagneux, S and Martin, DP and Wilkinson, RJ},
doi = {molbev/msx107},
journal = {Molecular Biology and Evolution},
pages = {1654--1668},
title = {The Influence of HIV on the Evolution of Mycobacterium tuberculosis},
url = {http://dx.doi.org/10.1093/molbev/msx107},
volume = {34},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - HIV significantly affects the immunological environment during tuberculosis coinfection, and therefore may influence the selective landscape upon which M. tuberculosis evolves. To test this hypothesis whole genome sequences were determined for 169 South African M. tuberculosis strains from HIV-1 coinfected and uninfected individuals and analyzed using two Bayesian codon-model based selection analysis approaches: FUBAR which was used to detect persistent positive and negative selection (selection respectively favoring and disfavoring nonsynonymous substitutions); and MEDS which was used to detect episodic directional selection specifically favoring nonsynonymous substitutions within HIV-1 infected individuals. Among the 25,251 polymorphic codon sites analyzed, FUBAR revealed that 189-fold more were detectably evolving under persistent negative selection than were evolving under persistent positive selection. Three specific codon sites within the genes celA2b, katG, and cyp138 were identified by MEDS as displaying significant evidence of evolving under directional selection influenced by HIV-1 coinfection. All three genes encode proteins that may indirectly interact with human proteins that, in turn, interact functionally with HIV proteins. Unexpectedly, epitope encoding regions were enriched for sites displaying weak evidence of directional selection influenced by HIV-1. Although the low degree of genetic diversity observed in our M. tuberculosis data set means that these results should be interpreted carefully, the effects of HIV-1 on epitope evolution in M. tuberculosis may have implications for the design of M. tuberculosis vaccines that are intended for use in populations with high HIV-1 infection rates.
AU  - Koch,AS
AU  - Brites,D
AU  - Stucki,D
AU  - Evans,JC
AU  - Seldon,R
AU  - Heekes,A
AU  - Mulder,N
AU  - Nicol,M
AU  - Oni,T
AU  - Mizrahi,V
AU  - Warner,DF
AU  - Parkhill,J
AU  - Gagneux,S
AU  - Martin,DP
AU  - Wilkinson,RJ
DO  - molbev/msx107
EP  - 1668
PY  - 2017///
SN  - 1537-1719
SP  - 1654
TI  - The Influence of HIV on the Evolution of Mycobacterium tuberculosis
T2  - Molecular Biology and Evolution
UR  - http://dx.doi.org/10.1093/molbev/msx107
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000402754400009&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/50727
VL  - 34
ER  -
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