Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: comparison with HIV envelope.

Dimitri Lavillette (1) , Rym Barbouche (2) , Yongxiu Yao , Bertrand Boson (1, 3) , Cosset François-Loïc (1, 3) , Ian M Jones , Emmanuel Fenouillet (2)

1 Virologie humaine
2 IP - Ingénierie des protéines
3 BLG - BioSciences Lyon-Gerland

The capacity of the surface glycoproteins of enveloped viruses to mediate virus/cell binding and membrane fusion requires a proper thiol/disulfide balance. Chemical manipulation of their redox state using reducing agents or free sulfhydryl reagents affects virus/cell interaction. Conversely, natural thiol/disulfide rearrangements often occur during the cell interaction to trigger fusogenicity, hence the virus entry. We examined the relationship between the redox state of the 20 cysteine residues of the SARS-CoV (severe acute respiratory syndrome coronavirus) Spike glycoprotein S1 subdomain and its functional properties. Mature S1 exhibited approximately 4 unpaired cysteines, and chemically reduced S1 displaying up to approximately 6 additional unpaired cysteines still bound ACE2 and enabled fusion. In addition, virus/cell membrane fusion occurred in the presence of sulfhydryl-blocking reagents and oxidoreductase inhibitors. Thus, in contrast to various viruses including HIV (human immunodeficiency virus) examined in parallel, the functions of the SARS-CoV Spike glycoprotein exhibit a significant and surprising independence of redox state, which may contribute to the wide host range of the virus. These data suggest clues for molecularly engineering vaccine immunogens.

Mots clés: Antigens; Epithelial Cells; HIV Antigens; Humans; Oxidation-Reduction; Protein Folding; SARS Virus; Sulfhydryl Compounds

Mots clés: Viral; Cell Culture Techniques; Cysteine; Membrane Fusion; Membrane Glycoproteins; Viral Envelope Proteins; Viral Vaccines

Domaines: Biochimie [q-bio.BM]

Dimitri Lavillette, Rym Barbouche, Yongxiu Yao, Bertrand Boson, Cosset François-Loïc, et al.. Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: comparison with HIV envelope.. Journal of Biological Chemistry, 2006, 281 (14), pp.9200-4. ⟨10.1074/jbc.M512529200⟩. ⟨hal-00135374⟩