Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas

Naomi L. Forrester, Joel O. Wertheim, Vivian G. Dugan, Albert J. Auguste, David Lin, A. Paige Adams, Rubing Chen, Rodion Gorchakov, Grace Leal, Jose G. Estrada-Franco, Jyotsna Pandya, Rebecca A. Halpin, Kumar Hari, Ravi Jain, Timothy B. Stockwell, Suman R. Das, David E. Wentworth, Martin D. Smith, Sergei L. Kosakovsky Pond, Scott C. Weaver

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149–973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors.

Original languageEnglish (US)
Article numbere0005693
JournalPLoS neglected tropical diseases
Issue number8
StatePublished - Aug 2017

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases


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