Indian Council of Medical Research-National Institute of Virology, Pune, Maharashtra, India.
Department of Veterinary Pathology, Krantisinh Nana Patil College of Veterinary Science, Shirwal, Maharashtra, India.
Sci Rep. 2020 Jul 28;10(1):12561. doi: 10.1038/s41598-020-67599-x.
The present manuscript deals with experimental infections of bonnet macaques (Macaca radiata) to study disease progression for better insights into the Kyasanur Forest Disease (KFD) pathogenesis and transmission. Experimentally, 10 monkeys were inoculated with KFD virus (KFDV) (high or low dose) and were regularly monitored and sampled for various body fluids and tissues at preset time points. We found that only 2 out of the 10 animals showed marked clinical signs becoming moribund, both in the low dose group, even though viremia, virus shedding in the secretions and excretions were evident in all inoculated monkeys. Anti-KFDV immunoglobulin (Ig)M antibody response was observed around a week after inoculation and anti-KFDV IgG antibody response after two weeks. Anaemia, leucopenia, thrombocytopenia, monocytosis, increase in average clotting time, and reduction in the serum protein levels were evident. The virus could be re-isolated from the skin during the viremic period. The persistence of viral RNA in the gastrointestinal tract and lymph nodes was seen up to 53 and 81 days respectively. Neuro-invasion was observed only in moribund macaques. Re-challenge with the virus after 21 days of initial inoculation in a monkey did not result in virus shedding or immune response boosting.
本手稿涉及对食蟹猴(Macaca radiata)进行实验性感染,以研究疾病进展,从而更深入地了解基孔肯雅热(KFD)的发病机制和传播。实验中,将 10 只猴子用基孔肯雅热病毒(KFDV)(高或低剂量)进行接种,并定期监测和采样各种体液和组织,在预设时间点进行采样。我们发现,尽管所有接种的猴子都出现了明显的病毒血症、分泌物和排泄物中的病毒脱落,但只有 2 只动物(均来自低剂量组)表现出明显的临床症状,濒死状态。接种后约一周观察到抗 KFDV 免疫球蛋白(Ig)M 抗体反应,两周后出现抗 KFDV IgG 抗体反应。出现贫血、白细胞减少、血小板减少、单核细胞增多症、平均凝血时间延长和血清蛋白水平降低。在病毒血症期间可从皮肤中重新分离出病毒。在胃肠道和淋巴结中分别观察到病毒 RNA 持续存在长达 53 天和 81 天。只有濒死的猴子才观察到神经入侵。在初次接种 21 天后,用病毒对猴子进行再挑战,没有导致病毒脱落或免疫反应增强。