Development of a Zika Virus Infection Model in Cynomolgus Macaques.
Development of a Zika Virus Infection Model in Cynomolgus Macaques.
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DOI：
10.3389/fmicb.2016.02028
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发表时间：
2016
影响因子：
5.2
通讯作者：
Rayner J
中科院分区：
文献类型：
--
作者：
Koide F;Goebel S;Snyder B;Walters KB;Gast A;Hagelin K;Kalkeri R;Rayner J
印度恒河猴（IRM）的供应有限是研究寨卡病毒（ZIKV）发病机制和评估非人类灵长类动物适当控制措施的瓶颈。为了解决这些问题，我们在此报告了 ZIKV 感染的毛里求斯食蟹猴 (MCM) 模型。简而言之，将 6 个 MCM（登革热和 ZIKV 血清阴性）分为三组，每组各有男性和女性，并用不同剂量的亚洲 [PRVABC59（波多黎各）或 FSS13025（柬埔寨）] 或非洲（IBH30656）谱系 ZIKV 分离株进行攻击。监测临床体征；在感染后不同时间（p.i），通过定量逆转录聚合酶链反应和中和抗体（Nab）评估生物体液（血清、唾液和尿液）和组织（睾丸和大脑）的病毒载量，并通过50%斑块减少中和试验（PRNT50）评估中和抗体（Nab）。 PRVABC59 诱导病毒血症直至第 10 天均可检测到，病毒载量峰值出现在注射后 2-3 天。第 30 天观察到间歇性病毒血症峰值，滴度达到 2.5 × 103 基因组/mL。在睾丸、尿液和唾液中观察到中等病毒载量。相比之下，FSS13025 诱导的病毒血症仅持续长达 6 天，并且在睾丸中可检测到病毒载量，但在尿液和唾液中未检测到病毒载量。检测到复发性病毒血症，但滴度低于 PRVABC59。 PRVABC59 或 FSS13025 的挑战导致 100% 血清转化；平均 PRNT50 滴度范围为 597 至 5179。IBH30656 未能在 MCM 中建立感染，这表明 MCM 容易感染亚洲谱系的 ZIKV 分离株，但不易感染来自非洲的 ZIKV 分离株。由于 MCM 和 IRM 模型之间双相病毒血症和 Nab 反应的相似性，MCM 可能是评估 ZIKV 疫苗和候选治疗药物的合适替代方案。
Limited availability of Indian rhesus macaques (IRM) is a bottleneck to study Zika virus (ZIKV) pathogenesis and evaluation of appropriate control measures in non-human primates. To address these issues, we report here the Mauritian cynomolgus macaque (MCM) model for ZIKV infection. In brief, six MCMs (seronegative for Dengue and ZIKV) were subdivided into three cohorts with a male and female each and challenged with different doses of Asian [PRVABC59 (Puerto Rico) or FSS13025 (Cambodia)] or African (IBH30656) lineage ZIKV isolates. Clinical signs were monitored; and biological fluids (serum, saliva, and urine) and tissues (testes and brain) were assessed for viral load by quantitative reverse transcription polymerase chain reaction and neutralizing antibodies (Nab) by 50% Plaque Reduction Neutralization Test (PRNT50) at various times post-infection (p.i). PRVABC59 induced viremia detectable up to day 10, with peak viral load at 2–3 days p.i. An intermittent viremia spike was observed on day 30 with titers reaching 2.5 × 103 genomes/mL. Moderate viral load was observed in testes, urine and saliva. In contrast, FSS13025 induced viremia lasting only up to 6 days and detectable viral loads in testes but not in urine and saliva. Recurrent viremia was detected but at lower titers compare to PRVABC59. Challenge with either PRVABC59 or FSS13025 resulted in 100% seroconversion; with mean PRNT50 titers ranging from 597 to 5179. IBH30656 failed to establish infection in MCM suggesting that MCM are susceptible to infection with ZIKV isolates of the Asian lineage but not from Africa. Due to the similarity of biphasic viremia and Nab responses between MCM and IRM models, MCM could be a suitable alternative for evaluation of ZIKV vaccine and therapeutic candidates.