Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.
Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.
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DOI：
10.1371/journal.ppat.1008949
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发表时间：
2020-11
期刊：
影响因子：
6.7
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Zheng H;Li H;Guo L;Liang Y;Li J;Wang X;Hu Y;Wang L;Liao Y;Yang F;Li Y;Fan S;Li D;Cui P;Wang Q;Shi H;Chen Y;Yang Z;Yang J;Shen D;Cun W;Zhou X;Dong X;Wang Y;Chen Y;Dai Q;Jin W;He Z;Li Q;Liu L
新冠肺炎已成为一种流行病，在全球范围内引发了高感染率的重症肺炎。为了更好地了解SARS-CoV-2引起的发病机制，我们开发了一个恒河猴模型来模拟通过鼻腔途径的自然感染，导致SARS-CoV-2病毒在鼻子和粪便中脱落长达27天。重要的是，我们观察到感染动物在5 - 7 dpi时明显的间质性肺炎的病理进展，病毒在下呼吸道和淋巴结广泛传播，并且在5 - 21 dpi期间持续检测到病毒RNA。在感染期间，T细胞的动力学反应被发现有助于COVID-19的进展。我们的研究结果表明，T细胞的抗病毒反应在感染后3天被抑制，这可能与pbmc中Treg细胞群的增加有关。此外，在肺组织中检测到两波细胞因子（TGF-α、IL-4、IL-6、GM-CSF、IL-10、IL-15、IL-1β）和趋化因子（MCP-1/CCL2、IL-8/CXCL8和MIP-1β/CCL4）的增加。我们从该模型收集的数据表明，除了观察病毒脱落和病理分析外，肺部T细胞反应和细胞因子/趋化因子的变化应作为COVID-19治疗和疫苗开发的评估参数。了解SARS-CoV-2引起的病理过程对促进疫苗评估和医疗至关重要。在该模型建立之前，几种SARS-CoV-2感染动物模型的重点是揭示病毒的脱落期、间质性肺炎的发生和病毒在呼吸道的传播。然而，缺乏描述SARS-CoV-2感染期间T细胞反应和局部免疫反应动力学的数据。在我们的恒河猴模型中，除了关注病毒脱落和与人类病例相似的间质性肺炎外，我们还观察了呼吸道T细胞亚群的反应和局部细胞因子/趋化因子的变化，这是成功建立COVID-19动物模型的重要评价参数。
The COVID-19 has emerged as an epidemic, causing severe pneumonia with a high infection rate globally. To better understand the pathogenesis caused by SARS-CoV-2, we developed a rhesus macaque model to mimic natural infection via the nasal route, resulting in the SARS-CoV-2 virus shedding in the nose and stool up to 27 days. Importantly, we observed the pathological progression of marked interstitial pneumonia in the infected animals on 5–7 dpi, with virus dissemination widely occurring in the lower respiratory tract and lymph nodes, and viral RNA was consistently detected from 5 to 21 dpi. During the infection period, the kinetics response of T cells was revealed to contribute to COVID-19 progression. Our findings implied that the antiviral response of T cells was suppressed after 3 days post infection, which might be related to increases in the Treg cell population in PBMCs. Moreover, two waves of the enhanced production of cytokines (TGF-α, IL-4, IL-6, GM-CSF, IL-10, IL-15, IL-1β), chemokines (MCP-1/CCL2, IL-8/CXCL8, and MIP-1β/CCL4) were detected in lung tissue. Our data collected from this model suggested that T cell response and cytokine/chemokine changes in lung should be considered as evaluation parameters for COVID-19 treatment and vaccine development, besides of observation of virus shedding and pathological analysis. Understanding of the pathologic process caused by SARS-CoV-2 is critical for promoting vaccine evaluations and medical treatment. Prior to the development of this model, several animal models of SARS-CoV-2 infection focused on revealing the virus shedding period, the development of interstitial pneumonia, and virus dissemination in respiratory tract. However, data describing the kinetics of the T cell response and local immune response during SARS-CoV-2 infection are lacking. Here, in our rhesus macaque model, in addition to focusing on virus shedding and interstitial pneumonia similar with human cases, we observed the response of T cell subsets and local cytokine/chemokine changes in respiratory tract regarded as the important evaluation parameters for a successful animal model of COVID-19.
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影响因子：
168.9
作者：
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通讯作者：
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168.9
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44.1
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