Logue Christopher H, Bosio Christopher F, Welte Thomas, Keene Kimberley M, Ledermann Jeremy P, Phillips Aaron, Sheahan Brian J, Pierro Dennis J, Marlenee Nicole, Brault Aaron C, Bosio Catharine M, Singh Amber J, Powers Ann M, Olson Ken E
Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Colorado State University, Fort Collins, CO 80523, USA.
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention (CDC), Fort Collins, CO 80521, USA.
J Gen Virol. 2009 Aug;90(Pt 8):1848-1858. doi: 10.1099/vir.0.008656-0. Epub 2009 Apr 29.
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 < or =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 10(3) 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 10(3) 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.
关于与西部马脑炎病毒（WEEV）相关的毒力病毒决定因素知之甚少。在此，我们在远交系CD1小鼠模型中分析了六种北美WEEV分离株。全基因组序列分析表明，这六种WEEV分离株之间的差异≤2.7%。然而，当小鼠皮下注射10³ 个感染性颗粒（p.f.u.）的每种病毒时，死亡率百分比和平均死亡时间（MTD）有显著差异。两种WEEV毒株，麦克米伦（McM）和帝国181（IMP），在基因组序列上是六种中差异最大的；McM在感染后5天导致100%的死亡率，而IMP未导致死亡。McM在脑中的滴度显著高于IMP。当通过气溶胶、鼻内或静脉途径给予McM和IMP时，也观察到了类似的毒力差异。当通过脑内接种给予每种病毒10³ 个p.f.u.时，McM的致死率为100%，MTD为1.9天；相比之下，IMP未导致死亡。通过不同途径感染后IMP在脑中的存在以及未观察到死亡情况证实IMP具有神经侵袭性但无神经毒性。基于发病率、死亡率、MTD、脑损伤严重程度、病毒分布模式、感染途径以及培养细胞感染的差异，McM和IMP分别被鉴定为高毒力和低毒力分离株。
