ACE2 can act as the secondary receptor in the FcγR-dependent ADE of SARS-CoV-2 infection

被引：27
作者：
Wang, Zai [3 ]
Deng, Tingting [3 ]
Zhang, Yulian [4 ,5 ]
Niu, Wenquan [3 ]
Nie, Qiangqiang [6 ]
Yang, Shengnan [1 ,2 ,7 ,8 ]
Liu, Peipei [1 ,2 ,9 ]
Pei, Pengfei [10 ]
Chen, Long [10 ]
Li, Haibo [1 ,2 ]
Cao, Bin [1 ,2 ,11 ,12 ]
机构：
[1] China Japan Friendship Hosp, Natl Clin Res Ctr Resp Dis, Ctr Resp Med, Dept Pulm & Crit Care Med, Beijing, Peoples R China
[2] Chinese Acad Med Sci, Inst Resp Med, Natl Ctr Resp Med, Beijing, Peoples R China
[3] China Japan Friendship Hosp, Inst Clin Med Sci, Beijing, Peoples R China
[4] Peking Univ, Dept Neurosurg, China Japan Friendship Sch Clin Med, Beijing, Peoples R China
[5] China Japan Friendship Hosp, Dept Neurosurg, Beijing, Peoples R China
[6] China Japan Friendship Hosp, Dept Cardiovasc Surg, Beijing, Peoples R China
[7] Harbin Med Univ, Harbin, Heilongjiang, Peoples R China
[8] Tianjin Chest Hosp, Dept Resp & Crit Care Med, 261 Taierzhuang South Rd, Tianjin, Peoples R China
[9] Chinese Acad Med Sci & Peking Union Med Coll, Grad Sch Peking Union Med Coll, Beijing, Peoples R China
[10] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing Key Lab Bioproc, Beijing, Peoples R China
[11] Capital Med Univ, Dept Resp Med, Beijing, Peoples R China
[12] Tsinghua Univ Peking Univ Joint Ctr Life Sci, Beijing, Peoples R China
来源：
ISCIENCE | 2022年 / 25卷 / 01期
基金：
国家重点研发计划;
关键词：
SPIKE PROTEIN; VIRUS-INFECTION; ENHANCEMENT; ANTIBODIES; CAPACITY; CELLS; CD4;
D O I：
10.1016/j.isci.2021.103720
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
It is unknown whether antibody-mediated enhancement (ADE) contributes to the pathogenesis of COVID-19, and the conditions for ADE needs to be elucidated. We demonstrated that without inducing an ACE2-independent ADE on Raji cells, the neutralizing antibody CB6, a mouse anti-S1 serum and convalescent plasma, induced ADE on cells expressing Fc gamma RIIA/CD32A and low levels of endogenous ACE2. ADE occurred at sub-neutralizing antibody concentrations, indicating that unneutralized S protein was required for ADE. The enhanced infectivity of 614G variant was higher than that of 614D wildtype in the presence of anti-bodies, further suggesting that ADE may be influenced by virus strains with different ACE2-binding affinity. Finally, knockdown of ACE2 or treatment with a fusion-inhibition peptide EK1C4 significantly reduced ADE. In conclusion, we identified an ADE mechanism mediated by neutralizing antibodies against SARS-CoV-2. ACE2 may act as a secondary receptor required for the antibody-and Fc gamma R-mediated enhanced entry of SARS-CoV-2.
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页数：20
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