Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, United States of America.
PLoS One. 2011 Apr 20;6(4):e18558. doi: 10.1371/journal.pone.0018558.
The severe acute respiratory syndrome (SARS) epidemic was characterized by increased pathogenicity in the elderly due to an early exacerbated innate host response. SARS-CoV is a zoonotic pathogen that entered the human population through an intermediate host like the palm civet. To prevent future introductions of zoonotic SARS-CoV strains and subsequent transmission into the human population, heterologous disease models are needed to test the efficacy of vaccines and therapeutics against both late human and zoonotic isolates. Here we show that both human and zoonotic SARS-CoV strains can infect cynomolgus macaques and resulted in radiological as well as histopathological changes similar to those seen in mild human cases. Viral replication was higher in animals infected with a late human phase isolate compared to a zoonotic isolate. While there were significant differences in the number of host genes differentially regulated during the host responses between the three SARS-CoV strains, the top pathways and functions were similar and only apparent early during infection with the majority of genes associated with interferon signaling pathways. This study characterizes critical disease models in the evaluation and licensure of therapeutic strategies against SARS-CoV for human use.
严重急性呼吸综合征（SARS）疫情的特点是老年人的致病性增加，这是由于早期过度的先天宿主反应。SARS-CoV 是一种人畜共患病病原体，通过中间宿主（如果子狸）进入人类种群。为了防止未来引入人畜共患的 SARS-CoV 株，并随后传播到人类群体中，需要使用异源疾病模型来测试针对晚期人类和人畜共患分离株的疫苗和疗法的疗效。在这里，我们表明，人类和人畜共患的 SARS-CoV 株都可以感染食蟹猴，并导致类似于轻度人类病例的影像学和组织病理学变化。感染晚期人类分离株的动物中的病毒复制量高于感染人畜共患分离株的动物。虽然在三种 SARS-CoV 株的宿主反应过程中差异调节的宿主基因数量存在显著差异，但顶级途径和功能相似，并且仅在感染早期出现，大多数与干扰素信号通路相关的基因都与干扰素信号通路相关。这项研究描述了用于评估和许可针对 SARS-CoV 的治疗策略的关键疾病模型，以供人类使用。
