Molecular determinants of mouse neurovirulence and mosquito infection for Western equine encephalitis virus.
Authors: Mossel Eric C, Ledermann Jeremy P, Phillips Aaron T, Borland Erin M, Powers Ann M, Olson Ken E
Journal: PloS one
Summary
Western equine encephalitis virus (WEEV) presents a curious epidemiological paradox: despite being an established recombinant pathogen, human and equine cases remain rare despite active transmission cycles. Mossel and colleagues investigated the molecular basis of this phenomenon by comparing two naturally occurring WEEV isolates—McMillan (highly lethal to mice; poor mosquito infectivity) and IMP-181 (avirulent to mice; highly infectious to mosquitoes)—using chimeric viruses to identify critical virulence determinants. The E2 glycoprotein proved essential to both phenotypes, with a single amino acid substitution at position 214 (arginine in IMP versus glutamine in McM) accounting for much of the differential virulence in mice; similar substitutions at positions 181 and 214 on the E2 protein governed mosquito infectivity. Crucially, these adaptive advantages operated as mutually exclusive traits—viral genotypes optimised for mammalian pathogenicity were epidemiologically "trapped" in less efficient vectors, whilst highly transmissible variants were attenuated in their vertebrate hosts. For equine practitioners, these findings underscore why WEEV remains predominantly a wildlife concern rather than a frequent clinical diagnosis, and highlight the molecular constraints that currently limit pandemic potential in this genus of arboviruses.
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Practical Takeaways
- •WEEV exists as two naturally occurring phenotypes: one highly lethal to mice but poorly transmitted by mosquitoes, and one readily transmitted but non-lethal—understanding this trade-off is critical for epidemiological risk assessment
- •The mutually exclusive virulence phenotypes suggest that equine WEE cases are unlikely despite mosquito transmission of WEEV, reducing perceived endemic risk in affected regions
- •Farriers and veterinarians working in WEEV endemic areas should recognize this viral biology when evaluating encephalitis cases, as clinical presentation may not correlate with local transmission rates
Key Findings
- •WEEV E2 glycoprotein position 214 is a critical determinant of mouse neurovirulence, with arginine (IMP) conferring low mortality (~0%) and glutamine (McM) associated with high mortality (~90-100%)
- •E2 amino acid positions 181 and 214 determine mosquito infectivity rates, with IMP-infected Culex tarsalis reaching ~80% infection versus McM at ~10%
- •Mouse virulence and mosquito infectivity phenotypes are mutually exclusive, controlled by the same viral loci on E2 glycoprotein
- •The molecular trade-off between mammalian neurovirulence and vector competence may explain the absence of human and equine WEE cases despite active virus transmission