SARS-CoV-2 accessory protein ORF8 decreases antibody-dependent cellular cytotoxicity
SARS-CoV-2 accessory protein ORF8 decreases antibody-dependent cellular cytotoxicity
Abstract SARS-CoV-2 Spike glycoprotein is the major target of host neutralizing antibodies and the most changing viral protein in the continuously emerging SARS-CoV-2 variants as a result of frequent viral evasion from host antibody responses. In addition, SARS-CoV-2 encodes multiple accessory proteins that modulate host antiviral immunity by different mechanisms. Among all SARS-CoV-2 accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. Strikingly, this decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.
Arduini Ariana、Bourassa Catherine、Beaudoin-Bussi¨¨res Guillaume、Pan Qinghua、Medjahed Halima、Gendron-Lepage Gabrielle、Wang Zhen、Richard Jonathan、Liang Chen、Finzi Andr¨|s
Lady Davis Institute, Jewish General Hospital||Department of Medicine, McGill UniversityCentre de Recherche du CHUMCentre de Recherche du CHUM||D¨|partement de Microbiologie, Infectiologie et Immunologie, Universit¨| de Montr¨|alLady Davis Institute, Jewish General HospitalCentre de Recherche du CHUMCentre de Recherche du CHUMLady Davis Institute, Jewish General HospitalCentre de Recherche du CHUM||D¨|partement de Microbiologie, Infectiologie et Immunologie, Universit¨| de Montr¨|alLady Davis Institute, Jewish General Hospital||Department of Medicine, McGill University||Department of Microbiology and Immunology, McGill UniversityCentre de Recherche du CHUM||D¨|partement de Microbiologie, Infectiologie et Immunologie, Universit¨| de Montr¨|al||Department of Microbiology and Immunology, McGill University
基础医学生物科学研究方法、生物科学研究技术分子生物学
CoronavirusSARS-CoV-2ORF8accessory proteinFc-mediated effector functionADCCmonocytesNK cellsCD16
Arduini Ariana,Bourassa Catherine,Beaudoin-Bussi¨¨res Guillaume,Pan Qinghua,Medjahed Halima,Gendron-Lepage Gabrielle,Wang Zhen,Richard Jonathan,Liang Chen,Finzi Andr¨|s.SARS-CoV-2 accessory protein ORF8 decreases antibody-dependent cellular cytotoxicity[EB/OL].(2025-03-28)[2025-05-14].https://www.biorxiv.org/content/10.1101/2022.03.30.486403.点此复制
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