Open AccessVirulence and pathogenesis of SARS-CoV-2 infection in rhesus macaques: A nonhuman primate model of COVID-19 progression
Author(s) -
Huiwen Zheng,
Heng Li,
Lei Guo,
Yan Liang,
Jing Li,
Xi Wang,
Yunzhang Hu,
Lichun Wang,
Yun Liao,
Fengmei Yang,
Yanyan Li,
Shengtao Fan,
Dandan Li,
Pingfang Cui,
Qingling Wang,
Hongzhe Shi,
Yanli Chen,
Zening Yang,
Jing Yang,
Shen Dong,
Cun Wei,
Xiaofang Zhou,
Xingqi Dong,
Yunchuan Wang,
Yong Chen,
Qing Dai,
Weihua Jin,
Zhanlong He,
Qihan Li,
Long-ding Liu
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008949
Subject(s) - virology , biology , immunology , pathogenesis , rhesus macaque , virus , chemokine , viral shedding , population , pneumonia , cytokine , immune system , medicine , environmental health
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.