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Journal of General Virology (2002), 83, 1419-1430.
© 2002 Society for General Microbiology


Animal: RNA Viruses

Increased positive selection pressure in persistent (SSPE) versus acute measles virus infections

Christopher H. Woelk1, Oliver G. Pybus1, Li Jin2, David W. G. Brown2 and Edward C. Holmes1

Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK1
Enteric, Respiratory and Neurological Virus Laboratory, Central Public Health Laboratory, London NW9 5HT, UK2

Author for correspondence: Christopher Woelk. Fax +44 1865 310447. e-mail Christopher.Woelk{at}zoo.ox.ac.uk

We compared the extent of positive selection acting on acute and persistent strains of measles virus (MV). Far stronger positive selection was found in the fusion (F) and haemagglutinin (H) genes from subacute sclerosing panencephalitis (SSPE) compared to acute MV cases. Most of the positively selected sites identified in these surface glycoprotein genes from SSPE cases correspond to structural, functional or antigenic areas, and could not be explained by the effects of cell passaging. The correlations between selected sites and functional studies of MV are discussed in detail with reference to the maintenance of persistent infection. No positive selection was found in the matrix (M) gene from acute cases of MV and the effects of including hypermutated SSPE M gene sequences in phylogenetic inference were also explored. Finally, using H gene data, we estimated the rate of molecular evolution for SSPE strains as 3·4x10-4 substitutions/site/year, which is similar to previous estimates obtained for acute strains.




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