Infectivity variation and genetic diversity among strains of Western equine encephalitis virus

Abstract

Variation in infectivity and genetic diversity in the structural proteins were compared among eight strains of Western equine encephalitis virus (WEEV) to investigate WEEV virulence at the molecular level. A lethal intranasal infectivity model of WEEV was developed in adult BALB/c mice. All eight strains examined were 100 % lethal to adult mice in this model, but they varied considerably in the time to death. Based on the time to death, the eight strains could be classified into two pathotypes: a high-virulence pathotype, consisting of strains California, Fleming and McMillan, and a low-virulence pathotype, comprising strains CBA87, Mn548, B11, Mn520 and 71V-1658. To analyse genetic diversity in the structural protein genes, 26S RNAs from these eight strains were cloned and sequenced and found to have >96 % nucleotide and amino acid identity. A cluster diagram divided the eight WEEV strains into two genotypes that matched the pathotype grouping exactly, suggesting that variation in infectivity can be attributed to genetic diversity in the structural proteins among these eight strains. Furthermore, potential amino acid differences in some positions between the two groups were identified, suggesting that these amino acid variations contributed to the observed differences in virulence.

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

“…Forrester et al (2008) demonstrated that only one of ten WEEV isolates (CR46) caused .50 % mortality in subcutaneously infected Swiss-Webster mice (age of mice not given). The MTD of IMP when infected via aerosol was 7 days, considerably longer than any of the isolates tested by Nagata et al (2006), and the survival rate was 90 %. Bianchi et al (1993) also infected outbred Swiss NIH mice (28-32 days old) with similar doses, but using the intracranial and intraperitoneal routes of infection, and showed that Virulence variation among WEE viruses in mice neuroinvasiveness was uniquely associated with epizootic strains of WEEV.…”

“…By using the intracranial and intraperitoneal routes, others have shown that enzootic isolates of WEEV from California were not uniformly of low pathogenicity and could show a range of virulence in adult mice (Hahn et al, 1988). Nagata et al (2006) reported 100 % mortality in each of eight isolates of WEEV by the intranasal route in adult BALB/c mice, although there was variation in MTD.…”

“…Whilst several pathogenesis studies have been carried out for both SINV and EEEV (Del Piero et al, 2001;Griffin, 1989;Hirsch & Griffin, 1979;Polo et al, 1988;Sherman & Griffin, 1990), the pathogenicity of WEEV remains relatively undescribed (Forrester et al, 2008;Fraizer et al, 1985;Gardner et al, 2008;Hardy et al, 1997;Julander et al, 2007;Nagata et al, 2006;Zlotnik et al, 1972). Nagata et al (2006) examined virulence of eight isolates of WEEV in adult female BALB/c mice infected via the intranasal route. All showed 100 % mortality and little variation in rate of onset of mortality.…”

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

“…6 Comparisons of isolates from North and South America reveal several antigenic subtypes and viral lineages, 7,8 with variation in virulence in rodent models of disease. [9][10][11] In North America, EEEV circulates between birds and Cx. melanura or other mosquitoes, but transmission to humans or horses can occur through Aedes, Coquillettidia, or Culex mosquito species that feed on both birds and mammals.…”

Encephalitic Development in Alphaviral Infection

“…Like in humans, age and strain of mouse infected, route of inoculations, and virulence of virus strain all influence the susceptibility of the host (Aguilar, 1970;Bianchi, et al, 1993;Logue, et al, 2009;Monath, et al, 1978;Nagata, et al, 2006). Peripheral routes of infection result in approximately 50% mortality with intracerebral (IC) or intranasal (IN) challenge resulting in more uniform, dose-dependent mortality depending on strain of virus and background of murine model (Hardy, et al, 1997;Julander, et al, 2007;Liu, et al, 1970).…”