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Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression

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 nos...

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Detalles Bibliográficos
Autores principales: Zheng, Huiwen, Li, Heng, Guo, Lei, Liang, Yan, Li, Jing, Wang, Xi, Hu, Yunguang, Wang, Lichun, Liao, Yun, Yang, Fengmei, Li, Yanyan, Fan, Shengtao, Li, Dandan, Cui, Pingfang, Wang, Qingling, Shi, Haijing, Chen, Yanli, Yang, Zening, Yang, Jinling, Shen, Dong, Cun, Wei, Zhou, Xiaofang, Dong, Xingqi, Wang, Yunchuan, Chen, Yong, Dai, Qing, Jin, Weihua, He, Zhanlong, Li, Qihan, Liu, Longding
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660522/
https://www.ncbi.nlm.nih.gov/pubmed/33180882
http://dx.doi.org/10.1371/journal.ppat.1008949
Descripción
Sumario: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.