Complete Genome Sequencing of a Collection of Eastern Equine Encephalitis Viruses (EEEV)

Eastern equine encephalitis virus (EEEV) is a mosquito-borne alphavirus (family,Togaviridae) of significant public and veterinary health importance throughout North,Central and South America. It has a single-stranded positive sense RNA genome of about 11,700 nt in length. EEEV causes a very debilitating disease in humans with case-fatality rates ranging between 50 and 75%, and for equids, rates can achieve rates as high as 80%. It is currently classified as a select agent on the NIAID category B list of priority pathogens, and was being developed for use as a potential bioweapon during the cold war. Despite hundreds of isolations and the significant public and veterinary health problem this virus poses, the majority of EEEV genetic studies primarily involved only partial gene sequences of the structural or non-structural genes and only 10 complete genomes have been determined and deposited on GenBank to date. In contrast to EEEV, extensive genetic studies have been performed on related alphaviruses, such as Venezuelan equine encephalitis and Chikungunya viruses, which has led to a detailed understanding of the mutations involved in emergence, genetic determinants of virulence and disease, and thorough characterization based on genealogy. In the absence of sufficient complete genome sequence data for EEEV, comparable studies cannot be performed thoroughly, and those few studies that relied on partial genomic fragments have already been very insightful in describing EEEV genetic diversity (Arrigo et al., 2010; Brault et al., 1999), positively selected amino acid sites (Arrigo et al., 2010), and mutations associated with certain phenotypes (Cooper and Scott, 2001; Weaver et al., 1999). The proposed project aims to fill this gap in sequence data by elucidating the complete genomes for 100 EEEV strains that represent the entire geographic and temporal distribution of EEEV since its first isolation in the new world in 1933.

The resultant genetic data generated in this study would allow researchers to (i) characterize EEEV genetic diversity and describe its molecular epidemiology; (ii) identify genetic determinants of EEEV emergence and virulence; (iii) infer the demographic history and evolutionary dynamics of EEEV; (iv) infer the evolution of virulence and pathogenesis throughout EEEV’s transmission history; (v) improve the ability to derive attenuated EEEV stains for vaccine development, (vi) generate infectious cDNA clones, and lastly; (vii) identify genetic factors underlying phenotypic differences among EEEV strains in the New World.

This project is proposed as a collaborative study between the NIAID Genome Sequencing Center, the University of Texas Medical Branch, The Connecticut Agricultural Experiment Station, South Florida University, Colorado State University, and the Division of Vector-Borne Diseases, and the Center for Disease Prevention and Control. We will ensure the generation of the best possible data set so further research in the aforementioned areas may be pursued without limitations. The data generated will also be useful for related alphavirus studies.

White Paper Access

The initial white paper submitted can be downloaded here. Since white papers are not always approved exactly as submitted, this document may not exactly describe the final form of the project. Please contact gsc@jcvi.org if you have any questions.

Funding