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
相关论文
共 35 条
  • [21] MONOCLONAL-ANTIBODIES TO THE SPIKE PROTEIN OF FELINE INFECTIOUS PERITONITIS VIRUS MEDIATE ANTIBODY-DEPENDENT ENHANCEMENT OF INFECTION OF FELINE MACROPHAGES
    OLSEN, CW
    CORAPI, WV
    NGICHABE, CK
    BAINES, JD
    SCOTT, FW
    [J]. JOURNAL OF VIROLOGY, 1992, 66 (02) : 956 - 965
  • [22] INFECTION OF MONOCYTES BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BLOCKED BY INHIBITORS OF CD4-GP120 BINDING, EVEN IN THE PRESENCE OF ENHANCING ANTIBODIES
    PERNO, CF
    BASELER, MW
    BRODER, S
    YARCHOAN, R
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (04) : 1043 - 1056
  • [23] Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses
    Qi, Furong
    Qian, Shen
    Zhang, Shuye
    Zhang, Zheng
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2020, 526 (01) : 135 - 140
  • [24] Fc glycans of therapeutic antibodies as critical quality attributes
    Reusch, Dietmar
    Tejada, Max L.
    [J]. GLYCOBIOLOGY, 2015, 25 (12) : 1325 - 1334
  • [25] Two Different Antibody-Dependent Enhancement (ADE) Risks for SARS-CoV-2 Antibodies
    Ricke, Darrell O.
    [J]. FRONTIERS IN IMMUNOLOGY, 2021, 12
  • [26] ROBINSON WE, 1988, LANCET, V1, P790
  • [27] Differential enhancement of dengue virus immune complex infectivity mediated by signaling-competent and signaling-incompetent human FcγRIA (CD64) or FcγRIIA (CD32)
    Rodrigo, W. W. Shanaka I.
    Jin, Xia
    Blackley, Shanley D.
    Rose, Robert C.
    Schlesinger, Jacob J.
    [J]. JOURNAL OF VIROLOGY, 2006, 80 (20) : 10128 - 10138
  • [28] A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2
    Shi, Rui
    Shan, Chao
    Duan, Xiaomin
    Chen, Zhihai
    Liu, Peipei
    Song, Jinwen
    Song, Tao
    Bi, Xiaoshan
    Han, Chao
    Wu, Lianao
    Gao, Ge
    Hu, Xue
    Zhang, Yanan
    Tong, Zhou
    Huang, Weijin
    Liu, William Jun
    Wu, Guizhen
    Zhang, Bo
    Wang, Lan
    Qi, Jianxun
    Feng, Hui
    Wang, Fu-Sheng
    Wang, Qihui
    Gao, George Fu
    Yuan, Zhiming
    Yan, Jinghua
    [J]. NATURE, 2020, 584 (7819) : 120 - +
  • [29] 2 RECEPTORS ARE REQUIRED FOR ANTIBODY-DEPENDENT ENHANCEMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION - CD4 AND FC-GAMMA-R
    TAKEDA, A
    SWEET, RW
    ENNIS, FA
    [J]. JOURNAL OF VIROLOGY, 1990, 64 (11) : 5605 - 5610
  • [30] Wan YS, 2020, J VIROL, V94, DOI [10.1128/JVI.02015-19, 10.1128/JVI.00127-20]
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