Significant redox insensitivity of the functions of the SARS-CoV spike glycoprotein: comparison with HIV envelope.
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.
Lavillette
Dimitri
D
INSERM U758, Ecole Normale Supérieure, Institut Fédératif de Recherche (IFR) 128, Lyon-Gerland F69007, Lyon, France.
Barbouche
Rym
R
Yao
Yongxiu
Y
Boson
Bertrand
B
Cosset
François-Loïc
FL
Jones
Ian M
IM
Fenouillet
Emmanuel
E
D000956:Antigens, Viral; D018929:Cell Culture Techniques; D003545:Cysteine / Q000737:chemistry; D004847:Epithelial Cells; D015488:HIV Antigens / Q000737:chemistry*; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry*; D010084:Oxidation-Reduction; D017510:Protein Folding; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity*; D064370:Spike Glycoprotein, Coronavirus; D013438:Sulfhydryl Compounds / Q000032:analysis; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014765:Viral Vaccines
D000956:Antigens, Viral; D015488:HIV Antigens; D008562:Membrane Glycoproteins; D064370:Spike Glycoprotein, Coronavirus; D013438:Sulfhydryl Compounds; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D003545:Cysteine