Experimental Zika Virus Inoculation in a New World Monkey Model Reproduces Key Features of the Human Infection.

Experimental Zika Virus Inoculation in a New World Monkey Model Reproduces Key Features of the Human Infection.
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DOI:
10.1038/s41598-017-17067-w
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发表时间:
2017-12-07
期刊:
影响因子:
4.6
通讯作者:
Patterson J
Patterson J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chiu CY;Sánchez-San Martín C;Bouquet J;Li T;Yagi S;Tamhankar M;Hodara VL;Parodi LM;Somasekar S;Yu G;Giavedoni LD;Tardif S;Patterson J

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寨卡病毒(ZIKV)感染的猴子模型是迫切需要的,以更好地了解传播和发病机制,因为它已被证明与孕妇的胎儿脑缺陷和急性神经系统疾病有关。在这里,我们用ZIKV(原型1947非洲株)实验性地感染了4只雄性绒猴,并通过对各种体液和组织进行取样对它们进行了近3个月的临床监测。我们表明,这些新世界猴中ZIKV急性感染的过程在许多方面与人类疾病相似,包括(1)在大多数情况下缺乏明显的临床症状,(2)病毒在体液如精液和唾液中的持续时间比血清中更长,以及(3)产生中和抗体以及抗病毒免疫宿主反应。重要的是,发现ZIKV感染的唾液样品(除了血清之外)具有感染性,表明通过口服途径进行病毒传播的潜在能力。用来自巴西的当代爆发菌株SPH2015对先前感染的绒猴进行再攻击,导致持续的抗感染保护,没有病毒脱落,并增强了免疫应答。考虑到与人类感染的关键相似性,ZIKV感染的绒猴模型可能有助于测试新药和疫苗。
A monkey model of Zika virus (ZIKV) infection is urgently needed to better understand transmission and pathogenesis, given its proven association with fetal brain defects in pregnant women and acute neurological illness. Here we experimentally infected 4 male marmosets with ZIKV (prototype 1947 African strain) and monitored them clinically with sampling of various body fluids and tissues for nearly 3 months. We show that the course of acute infection with ZIKV in these New World monkeys resembles the human illness in many respects, including (1) lack of apparent clinical symptoms in most cases, (2) persistence of the virus in body fluids such as semen and saliva for longer periods of time than in serum, and (3) generation of neutralizing antibodies as well as an antiviral immunological host response. Importantly, ZIKV-infected saliva samples (in addition to serum) were found to be infectious, suggesting potential capacity for viral transmission by the oral route. Re-challenge of a previously infected marmoset with a contemporary outbreak strain SPH2015 from Brazil resulted in continued protection against infection, no viral shedding, and boosting of the immune response. Given the key similarities to human infection, a marmoset model of ZIKV infection may be useful for testing of new drugs and vaccines.
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