JVI Accepts, published online ahead of print on 4 November 2009

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J. Virol. doi:10.1128/JVI.01738-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Yellow Fever Virus Exhibits Slower Evolutionary Dynamics Than Dengue Virus

Amadou A. Sall, Ousmane Faye, Mawlouth Diallo, Cadhla Firth, Andrew Kitchen, and Edward C. Holmes^*

Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220, Dakar, Senegal; Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA; Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA

^* To whom correspondence should be addressed. Email: ech15{at}psu.edu.

Although yellow fever has historically been one of the most important viral infections of humans, relatively little is known about the evolutionary processes that shape its genetic diversity. Similarly, there is limited information on the molecular epidemiology of yellow fever virus (YFV) in Africa, even though it most likely first emerged on this continent. Through an analysis of complete E gene sequences, including a newly acquired viral collection from central and west Africa (Senegal, Cameroon, Central African Republic, Côte d'Ivoire, Mali, and Mauritania), we show that YFV exhibits markedly lower rates of evolutionary change compared to dengue virus, despite numerous biological similarities between these two viruses. From this observation, along with a lack of clock-like evolutionary behavior in YFV, we suggest that vertical transmission, itself characterized by lower replication rates, may play an important role in the evolution of YFV in its enzootic setting. Despite a reduced rate of nucleotide substitution, phylogenetic patterns and estimates of times to common ancestry in YFV still accord well with the dual histories of colonialism and the slave trade, with areas of sylvatic transmission (such as Kedougou, Senegal) acting as enzootic/epidemic foci.