PMID- 34579572
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 2150-7511 (Electronic)
VI  - 12
IP  - 5
DP  - 2021 Oct 26
TI  - Antibody-Dependent Enhancement of SARS-CoV-2 Infection Is Mediated by the IgG 
      Receptors FcgammaRIIA and FcgammaRIIIA but Does Not Contribute to Aberrant Cytokine 
      Production by Macrophages.
PG  - e0198721
LID - 10.1128/mBio.01987-21 [doi]
LID - e01987-21
AB  - The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about the 
      detrimental effects of antibodies. Antibody-dependent enhancement (ADE) of 
      infection is one of the biggest concerns in terms of not only the antibody 
      reaction to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon 
      reinfection with the virus but also the reaction to COVID-19 vaccines. In this 
      study, we evaluated ADE of infection by using COVID-19 convalescent-phase plasma 
      and BHK cells expressing human Fcgamma receptors (FcgammaRs). We found that FcgammaRIIA and 
      FcgammaRIIIA mediated modest ADE of infection against SARS-CoV-2. Although ADE of 
      infection was observed in monocyte-derived macrophages infected with SARS-CoV-2, 
      including its variants, proinflammatory cytokine/chemokine expression was not 
      upregulated in macrophages. SARS-CoV-2 infection thus produces antibodies that 
      elicit ADE of infection, but these antibodies do not contribute to excess 
      cytokine production by macrophages. IMPORTANCE Viruses infect cells mainly via 
      specific receptors at the cell surface. Antibody-dependent enhancement (ADE) of 
      infection is an alternative mechanism of infection for viruses to infect immune 
      cells that is mediated by antibodies and IgG receptors (FcgammaRs). Because ADE of 
      infection contributes to the pathogenesis of some viruses, such as dengue virus 
      and feline coronavirus, it is important to evaluate the precise mechanism of ADE 
      and its contribution to the pathogenesis of SARS-CoV-2. Here, using 
      convalescent-phase plasma from COVID-19 patients, we found that two types of 
      FcgammaRs, FcgammaRIIA and FcgammaRIIIA, mediate ADE of SARS-CoV-2 infection. Although ADE of 
      infection was observed for SARS-CoV-2 and its recent variants, proinflammatory 
      cytokine production in monocyte-derived macrophages was not upregulated. These 
      observations suggest that SARS-CoV-2 infection produces antibodies that elicit 
      ADE of infection, but these antibodies may not be involved in aberrant cytokine 
      release by macrophages during SARS-CoV-2 infection.
FAU - Maemura, Tadashi
AU  - Maemura T
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA.
AD  - Division of Virology, The Institute of Medical Science, The University of Tokyo, 
      Tokyo, Japan.
FAU - Kuroda, Makoto
AU  - Kuroda M
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA.
FAU - Armbrust, Tammy
AU  - Armbrust T
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA.
FAU - Yamayoshi, Seiya
AU  - Yamayoshi S
AUID- ORCID: 0000-0001-7768-5157
AD  - Division of Virology, The Institute of Medical Science, The University of Tokyo, 
      Tokyo, Japan.
AD  - The Research Center for Global Viral Diseases, National Center for Global Health 
      and Medicine Research Institute, Tokyo, Japan.
FAU - Halfmann, Peter J
AU  - Halfmann PJ
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA.
FAU - Kawaoka, Yoshihiro
AU  - Kawaoka Y
AUID- ORCID: 0000-0001-5061-8296
AD  - Department of Pathobiological Sciences, School of Veterinary Medicine, University 
      of Wisconsin-Madison, Madison, Wisconsin, USA.
AD  - Division of Virology, The Institute of Medical Science, The University of Tokyo, 
      Tokyo, Japan.
AD  - The Research Center for Global Viral Diseases, National Center for Global Health 
      and Medicine Research Institute, Tokyo, Japan.
AD  - Department of Special Pathogens, International Research Center for Infectious 
      Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, 
      Japan.
LA  - eng
GR  - HHSN272201400008C/AI/NIAID NIH HHS/United States
GR  - JP21wm0125002/Japan Agency for Medical Research and Development (AMED)/
GR  - JP20fk0108527/Japan Agency for Medical Research and Development (AMED)/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210928
PL  - United States
TA  - mBio
JT  - mBio
JID - 101519231
RN  - 0 (Cytokines)
RN  - 0 (FCGR3A protein, human)
RN  - 0 (Fc gamma receptor IIA)
RN  - 0 (Receptors, IgG)
SB  - IM
MH  - Animals
MH  - Antibody-Dependent Enhancement/physiology
MH  - Cell Line
MH  - Cricetinae
MH  - Cytokines/*metabolism
MH  - Humans
MH  - Macrophages/*metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, IgG/genetics/*metabolism
MH  - SARS-CoV-2/*pathogenicity
PMC - PMC8546849
OTO - NOTNLM
OT  - ADE
OT  - COVID-19
OT  - FcgammaRIIA
OT  - FcgammaRIIIA
OT  - SARS-CoV-2
OT  - antibody-dependent enhancement
OT  - macrophages
EDAT- 2021/09/29 06:00
MHDA- 2021/11/30 06:00
PMCR- 2021/09/28
CRDT- 2021/09/28 05:29
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/11/30 06:00 [medline]
PHST- 2021/09/28 05:29 [entrez]
PHST- 2021/09/28 00:00 [pmc-release]
AID - mBio01987-21 [pii]
AID - mbio.01987-21 [pii]
AID - 10.1128/mBio.01987-21 [doi]
PST - ppublish
SO  - mBio. 2021 Oct 26;12(5):e0198721. doi: 10.1128/mBio.01987-21. Epub 2021 Sep 28.