Cynomolgus macaque as an animal model for severe acute respiratory syndrome.

Cynomolgus macaque as an animal model for severe acute respiratory syndrome.
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DOI:
10.1371/journal.pmed.0030149
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发表时间:
2006-05
期刊:
影响因子:
15.8
通讯作者:
Paragas J
Paragas J
中科院分区:
医学1区
文献类型:
--
作者:
Lawler JV;Endy TP;Hensley LE;Garrison A;Fritz EA;Lesar M;Baric RS;Kulesh DA;Norwood DA;Wasieloski LP;Ulrich MP;Slezak TR;Vitalis E;Huggins JW;Jahrling PB;Paragas J

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2002年和2003年出现的严重急性呼吸系统综合症(SARS)影响了全球健康并造成了重大经济混乱。需要足够的动物模型来研究 SARS 相关冠状病毒(SARS-CoV)感染的潜在发病机制并开发有效的疫苗和治疗方法。我们报告了感染 SARS-CoV 的非人灵长类动物 (NHP) 中可测量的临床疾病的首次发现。为了表征 NHP 中 SARS-CoV 感染的临床相关参数,我们将 SARS-CoV 感染给食蟹猴,分为三组:I 组在鼻孔和支气管中感染,II 组在鼻孔和结膜中感染,III 组通过静脉注射。第一组和第二组的非人类灵长类动物出现了轻度至中度的症状性疾病。所有 NHP 都显示出病毒复制的证据并产生了中和抗体。第一组和第二组的几只动物的胸部X光片显示单灶性或多灶性肺炎,在感染后第8天到第10天达到高峰。临床实验室测试没有显着改变。总体而言,通过粘膜途径接种比静脉内接种产生更明显的疾病。第一组动物中有一半感染了源自 SARS-CoV Urbani 株的重组传染性克隆 SARS-CoV。这种传染性克隆产生的疾病与野生型厄巴尼菌株没有区别。食蟹猴感染 SARS-CoV 后,并未出现大多数成人 SARS 病例中出现的严重疾病;然而,我们的结果表明与幼儿中常见的 SARS-CoV 感染的轻度综合征有相似之处。 Jason Paragas 及其同事报告了在感染导致 SARS 的病毒 SARS-CoV 的非人类灵长类动物中首次发现可测量的临床疾病。
The emergence of severe acute respiratory syndrome (SARS) in 2002 and 2003 affected global health and caused major economic disruption. Adequate animal models are required to study the underlying pathogenesis of SARS-associated coronavirus (SARS-CoV) infection and to develop effective vaccines and therapeutics. We report the first findings of measurable clinical disease in nonhuman primates (NHPs) infected with SARS-CoV. In order to characterize clinically relevant parameters of SARS-CoV infection in NHPs, we infected cynomolgus macaques with SARS-CoV in three groups: Group I was infected in the nares and bronchus, group II in the nares and conjunctiva, and group III intravenously. Nonhuman primates in groups I and II developed mild to moderate symptomatic illness. All NHPs demonstrated evidence of viral replication and developed neutralizing antibodies. Chest radiographs from several animals in groups I and II revealed unifocal or multifocal pneumonia that peaked between days 8 and 10 postinfection. Clinical laboratory tests were not significantly changed. Overall, inoculation by a mucosal route produced more prominent disease than did intravenous inoculation. Half of the group I animals were infected with a recombinant infectious clone SARS-CoV derived from the SARS-CoV Urbani strain. This infectious clone produced disease indistinguishable from wild-type Urbani strain. SARS-CoV infection of cynomolgus macaques did not reproduce the severe illness seen in the majority of adult human cases of SARS; however, our results suggest similarities to the milder syndrome of SARS-CoV infection characteristically seen in young children. Jason Paragas and colleagues report the first findings of measurable clinical disease in nonhuman primates infected with the virus that causes SARS, SARS-CoV.
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