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Antibody-dependent enhancement (ADE) of SARS-CoV-2 pseudoviral infection requires FcγRIIB and virus-antibody complex with bivalent interaction.
- Source :
- Communications Biology; 3/24/2022, Vol. 5 Issue 1, p1-9, 9p
- Publication Year :
- 2022
-
Abstract
- Understanding the underlying molecular mechanisms behind ADE of SARS-CoV-2 is critical for development of safe and effective therapies. Here, we report that two neutralizing mAbs, MW01 and MW05, could enhance the infection of SARS-CoV-2 pseudovirus on FcγRIIB-expressing B cells. X-ray crystal structure determination and S trimer-binding modeling showed that MW01 and MW05 could bind to RBDs in S trimer with both "up" and "down" states. While, the neutralizing mAb MW07, which has no ADE activity only binds to RBD in S trimer with "up" state. Monovalent MW01 and MW05 completely diminished the ADE activity compared with their bivalent counterparts. Moreover, both macropinocytosis and endocytosis are confirmed involving in ADE of SARS-CoV-2 pseudoviral infection. Blocking endosome transportation and lysosome acidification could inhibit the ADE activity mediated by MW05. Together, our results identified a novel ADE mechanism of SARS-CoV-2 pseudovirus in vitro, FcγRIIB-mediated uptake of SARS-CoV-2/mAb complex with bivalent interaction. By distinguishing between two types of neutralizing antibodies that either exhibit or lack antibody-dependent enhancement (ADE) activity, FcγRIIB and bivalent binding are shown to be required for ADE in SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 5
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 155956251
- Full Text :
- https://doi.org/10.1038/s42003-022-03207-0