Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation

Ting Gao; Mingdong Hu; Xiaopeng Zhang; Hongzhen Li; Lin Zhu; Hainan Liu; Qincai Dong; Zhang Zhang; Zhongyi Wang; Yong Hu; Yangbo Fu; Yanwen Jin; Kaitong Li; Songtao Zhao; Yongjiu Xiao; Shuping Luo; Lufeng Li; Lingfang Zhao; Junli Liu; Huailong Zhao; Yue Liu; Weihong Yang; Jing Peng; Xiaoyu Chen; Ping Li; Yaoning Liu; Yonghong Xie; Jibo Song; Lu Zhang; Qingjun Ma; Xiuwu Bian; Wei Chen; Xuan Liu; Qing Mao; Cheng Cao

The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.03. 29.20041962 doi: medRxiv preprint Fig. 3 . N proteins potentiate LPS-induced pneumonia in mice. (A) BALB/c mice (10 mice/group) were infected with 1×10 9 PFU Ad-SARS N/Ad-null or a saline control, and LPS (5 mg/kg) was given on the 6th days post infection (d.p.i.). Antibodies (200 μg/kg) or C1INH (4 mg/kg) was injected 30 min before LPS injection. The fatality of mice was noted. (B) Lung paraffin sections were analyzed by HE staining. (C) Mice were infected with 1×10 8 PFU Ad-SARS N/Ad-null, 5 and LPS (5 mg/kg) was given by on 6 d.p.i. Mice were sacrificed after LPS challenged for 6 hr. Frozen lung sections were stained with anti-C4b antibody. (D) SARS-CoV N and MASP-2 complex formation in frozen lung sections was measured by in situ PLA, as indicated by the red signals. Deposited C3 fragments were stained with FITC-labeled anti-C3c antibodies (green). Scale bar, 50 μm. (E) Mice were pre-infected with 1×10 9 PFU Ad-MERS N/Ad-null and treated 10 with LPS, anti-MASP-2 antibody or C1INH as mentioned above. The mice survival curve was plotted. (F) Masp2 -/and Masp2 +/+ C57BL/6N mice were infected N-expressing adenovirus and injected with LPS as mentioned above. The mice survival curve was plotted. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.