Imperial College London
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ProfessorMohamedShamji

Faculty of Medicine, National Heart & Lung Institute

Professor of Immunology and Allergy
 
 
 
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Contact

 

+44 (0)20 7594 3476m.shamji99 Website

 
 
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Location

 

Room 111Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Beirag:2023:10.3390/v15061269,
author = {Beirag, N and Varghese, PM and Neto, MM and Al, Aiyan A and Khan, HA and Qablan, M and Shamji, MH and Sim, RB and Temperton, N and Kishore, U},
doi = {10.3390/v15061269},
journal = {Viruses},
title = {Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein.},
url = {http://dx.doi.org/10.3390/v15061269},
volume = {15},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The complement system is a key component of the innate immune response to viruses and proinflammatory events. Exaggerated complement activation has been attributed to the induction of a cytokine storm in severe SARS-CoV-2 infection. However, there is also an argument for the protective role of complement proteins, given their local synthesis or activation at the site of viral infection. This study investigated the complement activation-independent role of C1q and C4b-binding protein (C4BP) against SARS-CoV-2 infection. The interactions of C1q, its recombinant globular heads, and C4BP with the SARS-CoV-2 spike and receptor binding domain (RBD) were examined using direct ELISA. In addition, RT-qPCR was used to evaluate the modulatory effect of these complement proteins on the SARS-CoV-2-mediated immune response. Cell binding and luciferase-based viral entry assays were utilised to assess the effects of C1q, its recombinant globular heads, and C4BP on SARS-CoV-2 cell entry. C1q and C4BP bound directly to SARS-CoV-2 pseudotype particles via the RBD domain of the spike protein. C1q via its globular heads and C4BP were found to reduce binding as well as viral transduction of SARS-CoV-2 spike protein expressing lentiviral pseudotypes into transfected A549 cells expressing human ACE2 and TMPRSS2. Furthermore, the treatment of the SARS-CoV-2 spike, envelope, nucleoprotein, and membrane protein expressing alphaviral pseudotypes with C1q, its recombinant globular heads, or C4BP triggered a reduction in mRNA levels of proinflammatory cytokines and chemokines such as IL-1β, IL-8, IL-6, TNF-α, IFN-α, and RANTES (as well as NF-κB) in A549 cells expressing human ACE2 and TMPRSS2. In addition, C1q and C4BP treatment also reduced SARS-CoV-2 pseudotype infection-mediated NF-κB activation in A549 cells expressing human ACE2 and TMPRSS2. C1q and C4BP are synthesised primarily by hepatocytes; however, they are also produced by macrophages, and alveolar type I
AU  - Beirag,N
AU  - Varghese,PM
AU  - Neto,MM
AU  - Al,Aiyan A
AU  - Khan,HA
AU  - Qablan,M
AU  - Shamji,MH
AU  - Sim,RB
AU  - Temperton,N
AU  - Kishore,U
DO  - 10.3390/v15061269
PY  - 2023///
TI  - Complement Activation-Independent Attenuation of SARS-CoV-2 Infection by C1q and C4b-Binding Protein.
T2  - Viruses
UR  - http://dx.doi.org/10.3390/v15061269
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37376569
VL  - 15
ER  -
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