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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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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. |
format | Online Article Text |
id | pubmed-7660522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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