Differential Neurovirulence of African and Asian Genotype Zika Virus Isolates in Outbred Immunocompetent Mice.

Differential Neurovirulence of African and Asian Genotype Zika Virus Isolates in Outbred Immunocompetent Mice.
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DOI:
10.4269/ajtmh.17-0263
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发表时间:
2017-11
期刊:
The American journal of tropical medicine and hygiene
影响因子:
--
通讯作者:
Brault AC
Brault AC
中科院分区:
其他
文献类型:
--
作者:
Duggal NK;Ritter JM;McDonald EM;Romo H;Guirakhoo F;Davis BS;Chang GJ;Brault AC

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尽管寨卡病毒在近70年前首次分离,但直到最近才与人类重大疾病暴发有关。最近还记录了几种严重的ZIKV病的表现,包括胎儿畸形,如小头畸形和成人的格林-巴利综合征。虽然主要通过蚊子传播,但ZIKV的性传播已被记录在案。最近发表的几种干扰素受体基因敲除小鼠模型已经证明了ZIKV诱导的疾病。在这里,近交系具有免疫能力的CD-1/ICR成年小鼠被评估为对颅内疾病的易感性(I.C.)和腹膜腔(I.P.)接种乌干达原型株(MR766;非洲型)、低传代塞内加尔株(DakAr41524;非洲型)和最近从波多黎各感染的旅行者分离的ZIKV株(PRVABC59;亚洲型)。在接种该疫苗的小鼠中未观察到发病率。如果剂量不超过6log10 pfu,则使用MR766或PRVABC59。相比之下,CD-1/ICR小鼠接种了I.C.对于MR766,ZIKV毒株显示出80%-100%的死亡率,这与年龄无关。通过I.C途径传播的DakAr41524毒株导致30%的死亡,波多黎各ZIKV毒株未能引起死亡,但确实在60%的小鼠中诱导了血清中和免疫反应。这些数据为评估不同ZIKV毒株的神经毒力决定因素提供了一个潜在的动物模型,也为评估候选疫苗的保护效果提供了一个潜在的免疫活性挑战模型。
Although first isolated almost 70 years ago, Zika virus (ZIKV; Flavivirus, Flaviviridae) has only recently been associated with significant outbreaks of disease in humans. Several severe ZIKV disease manifestations have also been recently documented, including fetal malformations, such as microcephaly, and Guillain–Barré syndrome in adults. Although principally transmitted by mosquitoes, sexual transmission of ZIKV has been documented. Recent publications of several interferon receptor knockout mouse models have demonstrated ZIKV-induced disease. Herein, outbred immunocompetent CD-1/ICR adult mice were assessed for susceptibility to disease by intracranial (i.c.) and intraperitoneal (i.p.) inoculation with the Ugandan prototype strain (MR766; African genotype), a low-passage Senegalese strain (DakAr41524; African genotype) and a recent ZIKV strain isolated from a traveler infected in Puerto Rico (PRVABC59; Asian genotype). Morbidity was not observed in mice inoculated by the i.p. route with either MR766 or PRVABC59 for doses up to 6 log10 PFU. In contrast, CD-1/ICR mice inoculated i.c. with the MR766 ZIKV strain exhibited an 80–100% mortality rate that was age independent. The DakAr41524 strain delivered by the i.c route caused 30% mortality, and the Puerto Rican ZIKV strain failed to elicit mortality but did induce a serum neutralizing immune response in 60% of mice. These data provide a potential animal model for assessing neurovirulence determinants of different ZIKV strains as well as a potential immunocompetent challenge model for assessing protective efficacy of vaccine candidates.
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