Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys.
Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys.
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DOI：
10.1186/1743-422x-8-135
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发表时间：
2011-03-24
期刊：
影响因子：
4.8
通讯作者：
Whitehead SS
中科院分区：
文献类型：
--
作者：
Bennett RS;Gresko AK;Murphy BR;Whitehead SS
塔希纳病毒(TAHV)是加州脑炎病毒(CEV)血清群(布尼亚病毒科)的人类病原体，流行于欧洲、亚洲和非洲。TAHV维持一个地方性生活史，几种蚊媒和野兔、兔子、刺猬和啮齿动物作为小型哺乳动物的放大宿主。人类TAHV感染发生在夏季和初秋，症状包括发烧、头痛、身体不适、结膜炎、咽炎和恶心。TAHV病可进展到中枢神经系统，尽管与相关的La Crosse病毒(LACV)不同，尚未有死亡报告。人类感染频繁，中和抗体存在于流行地区60%-80%的老年人口中。为了确定TAHV野生型的基因组序列，我们选择了26年来从蚊子身上收集的三个TAHV分离株。在这里，我们提供了塔塔病毒S、M和L三个片段的第一个完整序列。三株TAHV分离株基因组高度保守，核苷酸和氨基酸序列同源性均大于99%。为了确定与CEV血清组其他成员的遗传亲缘关系，我们比较了TAHV与LACV、雪兔病毒(SSHV)、詹姆斯敦峡谷病毒(JCV)和Inkoo病毒(INKV)的蛋白质序列。氨基酸比较，TAHV与SSHV最为相似，其次为LACV、JCV和INKV。GN蛋白序列保守程度最高，其次是L、N、GC、NSS和NSM。在一只断奶的瑞士韦伯斯特小鼠模型中，所有三种TAHV分离株都具有一致的神经毒力，但只有一种病毒具有神经侵袭性。在恒河猴身上，即使在没有病毒血症的情况下，病毒也具有高度的免疫原性。用猴子免疫血清进行的交叉中和研究表明，TAHV在抗原性上不同于北美病毒LACV和JCV。在此，我们报道了TAHV的第一个完整序列，并对新世界病毒LACV、SSHV和JCV与旧世界病毒TAHV和INKV进行了基因分析。使用在猴子中产生的针对TAHV、LACV和JCV的免疫血清，我们已经证明了CEV血清组内的交叉中和。这种交叉反应可能会使病毒鉴定变得复杂，特别是在JCV感染之后，这种感染会引起交叉中和LACV和TAHV的抗体。这些数据还表明，单一疫苗可以产生交叉中和抗体反应，这可能会从广泛的地理范围提供对CEV血清组病毒的保护。
Tahyna virus (TAHV) is a human pathogen of the California encephalitis virus (CEV) serogroup (Bunyaviridae) endemic to Europe, Asia, and Africa. TAHV maintains an enzootic life cycle with several species of mosquito vectors and hares, rabbits, hedgehogs, and rodents serving as small mammal amplifying hosts. Human TAHV infection occurs in summer and early fall with symptoms of fever, headache, malaise, conjunctivitis, pharyngitis, and nausea. TAHV disease can progress to CNS involvement, although unlike related La Crosse virus (LACV), fatalities have not been reported. Human infections are frequent with neutralizing antibodies present in 60-80% of the elderly population in endemic areas. In order to determine the genomic sequence of wild-type TAHV, we chose three TAHV isolates collected over a 26-year period from mosquitoes. Here we present the first complete sequence of the TAHV S, M, and L segments. The three TAHV isolates maintained a highly conserved genome with both nucleotide and amino acid sequence identity greater than 99%. In order to determine the extent of genetic relatedness to other members of the CEV serogroup, we compared protein sequences of TAHV with LACV, Snowshoe Hare virus (SSHV), Jamestown Canyon virus (JCV), and Inkoo virus (INKV). By amino acid comparison, TAHV was most similar to SSHV followed by LACV, JCV, and INKV. The sequence of the GN protein is most conserved followed by L, N, GC, NSS, and NSM. In a weanling Swiss Webster mouse model, all three TAHV isolates were uniformly neurovirulent, but only one virus was neuroinvasive. In rhesus monkeys, the virus was highly immunogenic even in the absence of viremia. Cross neutralization studies utilizing monkey immune serum demonstrated that TAHV is antigenically distinct from North American viruses LACV and JCV. Here we report the first complete sequence of TAHV and present genetic analysis of new-world viruses, LACV, SSHV, and JCV with old-world viruses, TAHV and INKV. Using immune serum generated in monkeys against TAHV, LACV, and JCV, we have demonstrated cross-neutralization within the CEV serogroup. Such cross reactivity may complicate virus identification, especially following JCV infection which elicited antibodies that cross neutralized both LACV and TAHV. These data also suggest that a single vaccine could generate a cross-neutralizing antibody response which may provide protection against CEV serogroup viruses from a wide geographic range.