Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice
Luo‐Yuan Xia, Zhenfei Wang, Cui Xiao-ming, Yuan-Guo Li, Run‐Ze Ye, Dai-Yun Zhu, Fangxu Li, Jie Zhang, Wenhao Wang, Mingzhu Zhang, Wan‐Ying Gao, Lian‐Feng Li, Tengcheng Que, Tiecheng Wang, Na Jia, Jia-Fu Jiang, Yuwei Gao, Wu‐Chun Cao
Abstract
. Here we report isolation and characterization of pangolin-CoV-HKU4-P251T, the genome sequence of which is closest to that of a coronavirus from the greater bamboo bat (Tylonycteris robustula) in Yunnan Province, China, with a 94.3% nucleotide identity. Pangolin-CoV-HKU4-P251T is able to infect human cell lines, and replicates more efficiently in cells that express human-dipeptidyl-peptidase-4 (hDPP4)-expressing and pangolin-DPP4-expressing cells than in bat-DPP4-expressing cells. After intranasal inoculation with pangolin-CoV-HKU4-P251, hDPP4-transgenic female mice are likely infected, showing persistent viral RNA copy numbers in the lungs. Progressive interstitial pneumonia developed in the infected mice, characterized by the accumulation of macrophages, and increase of antiviral cytokines, proinflammatory cytokines, and chemokines in lung tissues. These findings suggest that the pangolin-borne HKU4-related coronavirus has a potential for emerging as a human pathogen by using hDPP4.