SARS-CoV-2 integral membrane proteins shape the serological responses of patients with COVID-19

Sophie Martin,Christopher Heslan,Gwénaële Jégou,Leif A Eriksson,Matthieu Le Gallo,Vincent Thibault,Eric Chevet,Florence Godey,Tony Avril

doi:10.1016/j.isci.2021.103185

Sophie Martin, Christopher Heslan + Show 7 more

Open Access

https://doi.org/10.1016/j.isci.2021.103185

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Abstract

SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has elicited a unique mobilization of the scientific community to develop efficient tools to understand and combat the infection. Like other coronavirae, SARS-CoV-2 hijacks host cell secretory machinery to produce viral proteins that compose the nascent virions; including spike (S), envelope (E), and membrane (M) proteins, the most exposed transmembrane proteins to the host immune system. As antibody response is part of the anti-viral immune arsenal, we investigate the immunogenic potential of S, E, and M using a human cell-based system to mimic membrane insertion and N-glycosylation. Both S and M elicit specific Ig production in patients with SARS-CoV-2. Patients with moderate and severe diseases exhibit elevated Ig responses. Finally, reduced Ig binding was observed with spike G614 compared to D614 variant. Altogether, our assay points toward an unexpected immune response against M and represents a powerful tool to test humoral responses against actively evolving SARS-CoV-2 variants and vaccine effectiveness.

Highlights

The current coronavirus disease 2019 (COVID-19) pandemic has triggered unprecedented collective research efforts from the scientific community to better understand the disease and its cellular and molecular mechanisms to identify efficient therapeutic drugs for taking care of infected patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to develop vaccines for protecting the whole population from the infection (Hu et al, 2020; Poland et al, 2020; Sicari et al, 2020)
SUMMARY Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has elicited a unique mobilization of the scientific community to develop efficient tools to understand and combat the infection
As antibody response is part of the anti-viral immune arsenal, we investigate the immunogenic potential of S, E, and M using a human cell-based system to mimic membrane insertion and N-glycosylation

Summary

Introduction

The current coronavirus disease 2019 (COVID-19) pandemic has triggered unprecedented collective research efforts from the scientific community to better understand the disease and its cellular and molecular mechanisms to identify efficient therapeutic drugs for taking care of infected patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to develop vaccines for protecting the whole population from the infection (Hu et al, 2020; Poland et al, 2020; Sicari et al, 2020). Among the anti-viral immune responses elicited in infected patients, immunoglobulin (Ig) responses against viral transmembrane proteins expressed at the surface of the virus envelope are important for generating antibodies that limit virus propagation This occurs by preventing interactions with host cells, i.e., production of neutralizing antibodies that block the binding of the viral transmembrane spike protein to its receptor angiotensin-converting enzyme 2 (ACE2) expressed by infected host cells (Poland et al, 2020; Lan et al, 2020; Hoffmann et al, 2020; Zohar and Alter, 2020). These anti-virus antibodies are key mediators to trigger antibody-dependent immune responses such as the complement-dependent cytotoxicity as part of the humoral response (Zohar and Alter, 2020) or the antibody-dependent cellular cytotoxicity mediated by immune cells harboring Fc receptors such as NK lymphocytes, macrophages, and granulocytes to allow phagocytosis and destruction of the virus (Zohar and Alter, 2020)

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