DEVELOPMENT OF CHIMERIC VENEZUELAN EQUINE ENCEPHALITIS VIRUSES TO COMPARE THE ROLL OF NONSTRUCTURAL AND STRUCTURAL PROTEINS DURING INFECTION OF THE ENZOOTIC MOSQUITO VECTOR, CULEX TAENIOPUS

Joanie Kenney, MPH, R.Gorchakov, M.S., S. Weaver, Ph.D.

Department of Pathology, UTMB

Background: Venezuelan equine encephalitis generally exists in two ecological cycles: enzootic and epizootic. Viral strains that circulate in the enzootic cycle (ID and IE) are maintained in rodents and mosquito vectors and are typically unable to cause disease in equids. Epizootic viruses (IAB and IC) are able to infect equids and persist in a replication cycle between equids and epizootic mosquito vectors. Objective: While previous studies indicate that regions within the E2 glycoprotein are responsible for equine virulence, recent studies comparing epizootic and enzootics viruses in Culex taeniopus suggest that there might be regions outside of the structural regions that play a role in determining the viral phenotype. We hypothesize that regions of the nonstructural polyprotein also contribute to viral fitness during infection of enzootic vectors. Methods: To evaluate our hypothesis, we generated chimeric VEEV viruses between epizootic (IAB Trinidad Donkey) and enzootic (IE 68U201) viruses to compare the role of structural and nonstructural genes. Results: Upon analysis, previously developed IAB/IE and IE/IAB chimeras were found to have a faulty T7 promoter, 4 non-synonymous mutations, and a 3’UTR that did not match other cis-acting elements in the viral genomes. Conclusions: At this point, it is necessary to correct these errors before continuing with experiments. Supported by the Department of Pathology, NIAID RCE U54 AIO57156 and a McLaughlin fellowship.