Prasad Abhishek N, Woolsey Courtney, Geisbert Joan B, Agans Krystle N, Borisevich Viktoriya, Deer Daniel J, Mire Chad E, Cross Robert W, Fenton Karla A, Broder Christopher C, Geisbert Thomas W
Galveston National Laboratory, University of Texas Medical Branch, Galveston.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston.
J Infect Dis. 2020 May 11;221(Suppl 4):S436-S447. doi: 10.1093/infdis/jiz613.
The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are capable of causing severe and often lethal respiratory and/or neurologic disease in animals and humans. Given the sporadic nature of henipavirus outbreaks, licensure of vaccines and therapeutics for human use will likely require demonstration of efficacy in animal models that faithfully reproduce the human condition. Currently, the African green monkey (AGM) best mimics human henipavirus-induced disease.
The pathogenic potential of HeV and both strains of NiV (Malaysia, Bangladesh) was assessed in cynomolgus monkeys and compared with henipavirus-infected historical control AGMs. Multiplex gene and protein expression assays were used to compare host responses.
In contrast to AGMs, in which henipaviruses cause severe and usually lethal disease, HeV and NiVs caused only mild or asymptomatic infections in macaques. All henipaviruses replicated in macaques with similar kinetics as in AGMs. Infection in macaques was associated with activation and predicted recruitment of cytotoxic CD8+ T cells, Th1 cells, IgM+ B cells, and plasma cells. Conversely, fatal outcome in AGMs was associated with aberrant innate immune signaling, complement dysregulation, Th2 skewing, and increased secretion of MCP-1.
The restriction factors identified in macaques can be harnessed for development of effective countermeasures against henipavirus disease.
亨尼帕病毒，包括亨德拉病毒（HeV）和尼帕病毒（NiV），能够在动物和人类中引发严重且往往致命的呼吸道和/或神经系统疾病。鉴于亨尼帕病毒爆发具有散发性，人类用疫苗和治疗药物的获批可能需要在能如实再现人类病情的动物模型中证明其有效性。目前，非洲绿猴（AGM）最能模拟人类亨尼帕病毒引发的疾病。
在食蟹猴中评估了HeV以及两种NiV毒株（马来西亚株、孟加拉国株）的致病潜力，并与感染亨尼帕病毒的历史对照AGM进行比较。采用多重基因和蛋白质表达分析来比较宿主反应。
与AGM不同，在AGM中亨尼帕病毒会引发严重且通常致命的疾病，而HeV和NiV在猕猴中仅引起轻度或无症状感染。所有亨尼帕病毒在猕猴中的复制动力学与在AGM中相似。猕猴感染与细胞毒性CD8 + T细胞、Th1细胞、IgM + B细胞和浆细胞的激活及预测的募集有关。相反，AGM的致命结局与异常的固有免疫信号传导、补体失调、Th2偏向以及MCP - 1分泌增加有关。
在猕猴中鉴定出的限制因素可用于开发针对亨尼帕病毒疾病的有效对策。
