Genotypic analysis of two hypervariable human cytomegalovirus genes

Bradley, A.J. et al. (2008) Genotypic analysis of two hypervariable human cytomegalovirus genes. Journal of Medical Virology, 80(9), pp. 1615-1623. (doi:10.1002/jmv.21241) (PMID:18649324) (PMCID:PMC2658010)

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Abstract

Most human cytomegalovirus (HCMV) genes are highly conserved in sequence among strains, but some exhibit a substantial degree of variation. Two of these genes are UL146, which encodes a CXC chemokine, and UL139,which is predicted to encode a membrane glycoprotein. The sequences of these genes were determined from a collection of 184 HCMV samples obtained from Africa, Australia, Asia, Europe, and North America. UL146 is hypervariable throughout, whereas variation in UL139 is concentrated in a sequence encoding a potentially highly glycosylated region. The UL146 sequences fell into 14 genotypes, as did all previously reported sequences. The UL139 sequences grouped into 8 genotypes, and all previously reported sequences fell into a subset of these. There were minor differences among continents in genotypic frequencies for UL146 and UL139, but no clear geographical separation, and identical nucleotide sequences were represented among communities distant from each other. The frequent detection of multiple genotypes indicated that mixed infections are common. For both genes, the degree of divergence was sufficient to preclude reliable sequence alignments between genotypes in the most variable regions, and the mode of evolution involved in generating the genotypes could not be discerned. Within genotypes, constraint appears to have been the predominant mode, and positive selection was detected marginally at best. No evidence was found for linkage disequilibrium. The emerging scenario is that the HCMV genotypes developed in early human populations (or even earlier), becoming established via founder or bottleneck effects, and have spread, recombined and mixed worldwide in more recent times.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Geddes, Dr Colin and Carman, Professor William and Dargan, Dr Derrick and Gatherer, Dr Derek and Davison, Professor Andrew
Authors: Bradley, A.J., Kovacs, I.J., Gatherer, D., Dargan, D.J., Alkharsah, K.R., Chan, P.K.S., Carman, W.F., Dedicoat, M., Emery, V.C., Geddes, C.C., Gerna, G., Ben Ismaeil, B., Kaye, S., McGregor, A., Moss, P.A., Pusztai, R., Rawlinson, W.D., Scott, G.M., Wilkinson, G.W.G., Schulz, T.F., and Davison, A.J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Journal of Medical Virology
Publisher:John Wiley & Sons Ltd.
ISSN:0146-6615
ISSN (Online):1096-9071
Published Online:22 July 2008
Copyright Holders:Copyright © 2008 WILEY-LISS
First Published:First published in Journal of Medical Virology 80(9):1615-1623
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656321Genomics of human cytomegalovirusAndrew DavisonMedical Research Council (MRC)MC_UU_12014/3MVLS III - CENTRE FOR VIRUS RESEARCH