Zika viral dynamics and shedding in rhesus and cynomolgus macaques.
Zika viral dynamics and shedding in rhesus and cynomolgus macaques.
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DOI：
10.1038/nm.4206
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发表时间：
2016-12
期刊：
影响因子：
82.9
通讯作者：
Whitney JB
中科院分区：
文献类型：
--
作者：
Osuna CE;Lim SY;Deleage C;Griffin BD;Stein D;Schroeder LT;Omange RW;Best K;Luo M;Hraber PT;Andersen-Elyard H;Ojeda EF;Huang S;Vanlandingham DL;Higgs S;Perelson AS;Estes JD;Safronetz D;Lewis MG;Whitney JB
寨卡病毒感染与严重的神经系统并发症和胎儿畸形有关。然而，对病毒感染、复制和脱落的动力学知之甚少。在这里，我们表明恒河猴和食蟹猴都非常容易受到与美洲密切相关或目前在美洲流行的寨卡病毒谱系的感染。皮下接种病毒后，血浆中病毒RNA的检测早在感染后1d。在唾液、尿液、脑脊液（CSF）和精液中也检测到病毒RNA，但在阴道分泌物中为一过性。虽然病毒RNA在原发性感染清除血浆和尿液中的10天内，病毒RNA可检测到唾液和精液中，直到研究结束后，3周后，在血液中的病毒血症的决议。控制血液中的原发性寨卡病毒感染与快速的先天性和适应性免疫反应相关。我们还在感染的早期和晚期发现了组织中的寨卡RNA，包括大脑和男性和女性生殖组织。在初次感染后45天，用异源毒株再次感染6只动物，导致完全保护，这表明初次寨卡病毒感染产生保护性免疫。寨卡病毒早期侵入健康动物的神经系统，以及唾液和精液中脱落的程度和持续时间，强调了对人类其他神经系统并发症和非节肢动物介导传播的可能担忧。
Infection with Zika virus has been associated with serious neurological complications and fetal abnormalities. However, the dynamics of viral infection, replication and shedding are poorly understood. Here we show that both rhesus and cynomolgus macaques are highly susceptible to infection by lineages of Zika virus that are closely related to, or are currently circulating in, the Americas. After subcutaneous viral inoculation, viral RNA was detected in blood plasma as early as 1 d after infection. Viral RNA was also detected in saliva, urine, cerebrospinal fluid (CSF) and semen, but transiently in vaginal secretions. Although viral RNA during primary infection was cleared from blood plasma and urine within 10 d, viral RNA was detectable in saliva and seminal fluids until the end of the study, 3 weeks after the resolution of viremia in the blood. The control of primary Zika virus infection in the blood was correlated with rapid innate and adaptive immune responses. We also identified Zika RNA in tissues, including the brain and male and female reproductive tissues, during early and late stages of infection. Re-infection of six animals 45 d after primary infection with a heterologous strain resulted in complete protection, which suggests that primary Zika virus infection elicits protective immunity. Early invasion of Zika virus into the nervous system of healthy animals and the extent and duration of shedding in saliva and semen underscore possible concern for additional neurologic complications and nonarthropod-mediated transmission in humans.