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- Title
Virulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression.
- Authors
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
- Abstract
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. Author summary: 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.
- Subjects
COVID-19; RHESUS monkeys; SARS-CoV-2; MACAQUES; COVID-19 treatment; VIRAL shedding
- Publication
PLoS Pathogens, 2020, Vol 16, Issue 11, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1008949