High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species
High susceptibility, viral dynamics and persistence of South American Zika virus in New World monkey species
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DOI：
10.1038/s41598-019-50918-2
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发表时间：
2019-10-10
影响因子：
4.6
通讯作者：
Almond, Neil
中科院分区：
文献类型：
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作者：
Berry, Neil;Ferguson, Deborah;Almond, Neil
南美寨卡病毒（ZIKV）最近成为一种新型人类病原体，与神经系统疾病有关。然而，缺乏新世界灵长类动物中的比较ZIKV感染性研究。Callitrichidae家族的两个成员，普通绒猴（Callithrixjacchus）和红腹绢毛猴（Saguinus labiatus），对波多黎各来源的ZIKV（PRVABC 59）毒株的皮下攻击高度敏感。两者都表现出快速，高，急性病毒血症与早期神经浸润（3天）在外周和中枢神经组织。血液和组织中的ZIKV RNA水平在新世界宿主中显著高于旧世界物种（猕猴（Macaca mulatta）、食蟹猴（Macaca fascicularis））。绢毛猴和恒河猴表现出封闭带-1（Z 0 -1）染色的损失，表明ZIKV暴露后3天血脑屏障受损。在新世界和旧世界谱系中，在100天后，在远离接种部位的多个解剖部位的早期广泛传播先于广泛的ZIKV持续存在，特别是淋巴、神经和生殖部位。在脑组织中的延长的持续性对以其他方式解决的人ZIKV感染具有影响。不同的新世界物种的高易感性强调了ZIKV流行地区原生灵长类动物中ZIKV森林循环的可能建立。绢毛猴和绒猴代表了用于ZIKV发病机制和治疗干预研究的可行的新世界模型，包括使用当代菌株的疫苗。
South American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrixjacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKV(PRVABC59) strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.