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Virulence variation among isolates of western equine encephalitis virus in an outbred mouse model

Christopher H. Logue^1,2,

¹ Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA
² Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA
³ Center for Vector-Borne Diseases, University of California, Davis, CA, USA
⁴ Veterinary Sciences Centre, University College Dublin, Belfield, Dublin 4, Ireland

Correspondence
Christopher H. Logue
clogue{at}dstl.gov.uk

Little is known about viral determinants of virulence associated with western equine encephalitis virus (WEEV). Here, we have analysed six North American WEEV isolates in an outbred CD1 mouse model. Full genome sequence analyses showed 2.7 % divergence among the six WEEV isolates. However, the percentage mortality and mean time to death (MTD) varied significantly when mice received subcutaneous injections of 10³ p.f.u. of each virus. Two WEEV strains, McMillan (McM) and Imperial 181 (IMP), were the most divergent of the six in genome sequence; McM caused 100 % mortality by 5 days post-infection, whereas IMP caused no mortality. McM had significantly higher titres in the brain than IMP. Similar differences in virulence were observed when McM and IMP were administered by aerosol, intranasal or intravenous routes. McM was 100 % lethal with an MTD of 1.9 days when 10³ p.f.u. of each virus was administered by intracerebral inoculation; in contrast, IMP caused no mortality. The presence of IMP in the brains after infection by different routes and the lack of observed mortality confirmed that IMP is neuroinvasive but not neurovirulent. Based on morbidity, mortality, MTD, severity of brain lesions, virus distribution patterns, routes of infection and differences in infection of cultured cells, McM and IMP were identified as high- and low-virulence isolates, respectively.

Present address: Biomedical Sciences Department, Defence, Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.

The GenBank/EMBL/DDBJ accession numbers for the full genome sequences of WEEV isolates determined in this study are GQ287640–GQ287647.

Two supplementary tables, listing oligonucleotides used for full genome sequencing and numbers of unique isolate-specific amino acid and nucleotide changes of seven WEEV isolates, are available with the online version of this paper.

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