The Effect of Select SARS-CoV-2 N-Linked Glycan and Variant of Concern Spike Protein Mutations on C-Type Lectin-Receptor-Mediated Infection

Arjan Bains; Wenyan Guan; Patricia J LiWang

doi:10.3390/v15091901

The Effect of Select SARS-CoV-2 N-Linked Glycan and Variant of Concern Spike Protein Mutations on C-Type Lectin-Receptor-Mediated Infection

Viruses. 2023 Sep 9;15(9):1901. doi: 10.3390/v15091901.

Authors

Arjan Bains¹, Wenyan Guan², Patricia J LiWang³

Affiliations

¹ Chemistry and Biochemistry, University of California Merced, 5200 North Lake Rd., Merced, CA 95343, USA.
² Materials and Biomaterials Science and Engineering, University of California Merced, 5200 North Lake Rd., Merced, CA 95343, USA.
³ Molecular Cell Biology, Health Sciences Research Institute, University of California Merced, 5200 North Lake Rd., Merced, CA 95343, USA.

Abstract

The SARS-CoV-2 virion has shown remarkable resilience, capable of mutating to escape immune detection and re-establishing infectious capabilities despite new vaccine rollouts. Therefore, there is a critical need to identify relatively immutable epitopes on the SARS-CoV-2 virion that are resistant to future mutations the virus may accumulate. While hACE2 has been identified as the receptor that mediates SARS-CoV-2 susceptibility, it is only modestly expressed in lung tissue. C-type lectin receptors like DC-SIGN can act as attachment sites to enhance SARS-CoV-2 infection of cells with moderate or low hACE2 expression. We developed an easy-to-implement assay system that allows for the testing of SARS-CoV-2 trans-infection. Using our assay, we assessed how SARS-CoV-2 Spike S1-domain glycans and spike proteins from different strains affected the ability of pseudotyped lentivirions to undergo DC-SIGN-mediated trans-infection. Through our experiments with seven glycan point mutants, two glycan cluster mutants and four strains of SARS-CoV-2 spike, we found that glycans N17 and N122 appear to have significant roles in maintaining COVID-19's infectious capabilities. We further found that the virus cannot retain infectivity upon the loss of multiple glycosylation sites, and that Omicron BA.2 pseudovirions may have an increased ability to bind to other non-lectin receptor proteins on the surface of cells. Taken together, our work opens the door to the development of new therapeutics that can target overlooked epitopes of the SARS-CoV-2 virion to prevent C-type lectin-receptor-mediated trans-infection in lung tissue.

Keywords: C-type lectin receptor; COVID-19; DC-SIGN; N-linked glycans; SARS-CoV-2; trans-infection; variants of concern.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

COVID-19*
Epitopes
Humans
Lectins, C-Type / genetics
Mutation
Polysaccharides
SARS-CoV-2* / genetics
Spike Glycoprotein, Coronavirus / genetics

Substances

spike protein, SARS-CoV-2
Spike Glycoprotein, Coronavirus
Epitopes
Lectins, C-Type
Polysaccharides

Grants and funding

This research was funded by the Army Research Office, grant number W911NF2010268. A research fellowship for A.B. was provided by the NSF-CREST Center for Cellular and Biomolecular Machines (CCBM), grant number 2112675. Additional funding was from the COVID-19 funding program of the Health Science Research Institute at U.C. Merced.