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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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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
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author 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
author_facet 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
author_sort Zheng, Huiwen
collection PubMed
description 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.
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spelling pubmed-76605222020-11-18 Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression 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 PLoS Pathog Research Article 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. Public Library of Science 2020-11-12 /pmc/articles/PMC7660522/ /pubmed/33180882 http://dx.doi.org/10.1371/journal.ppat.1008949 Text en © 2020 Zheng et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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
Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title_full Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title_fullStr Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title_full_unstemmed Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title_short Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
title_sort virulence and pathogenesis of sars-cov-2 infection in rhesus macaques: a nonhuman primate model of covid-19 progression
topic Research Article
url 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
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