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Evasion of antibody neutralization in emerging severe acute respiratory syndrome coronaviruses.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Jan 18; Vol. 102 (3), pp. 797-801. Date of Electronic Publication: 2005 Jan 10. - Publication Year :
- 2005
-
Abstract
- Molecular characterization of the severe acute respiratory syndrome coronavirus has revealed genetic diversity among isolates. The spike (S) glycoprotein, the major target for vaccine and immune therapy, shows up to 17 substitutions in its 1,255-aa sequence; however, the biologic significance of these changes is unknown. Here, the functional effects of S mutations have been determined by analyzing their affinity for a viral receptor, human angiotensin-converting enzyme 2 (hACE-2), and their sensitivity to Ab neutralization with viral pseudotypes. Although minor differences among eight strains transmitted during human outbreaks in early 2003 were found, substantial functional changes were detected in S derived from a case in late 2003 from Guangdong province [S(GD03T0013)] and from two palm civets, S(SZ3) and S(SZ16). S(GD03T0013) depended less on the hACE-2 receptor and was markedly resistant to Ab inhibition. Unexpectedly, Abs that neutralized most human S glycoproteins enhanced entry mediated by the civet virus S glycoproteins. The mechanism of enhancement involved the interaction of Abs with conformational epitopes in the hACE-2-binding domain. Finally, improved immunogens and mAbs that minimize this complication have been defined. These data show that the entry of severe acute respiratory syndrome coronaviruses can be enhanced by Abs, and they underscore the need to address the evolving diversity of this newly emerged virus for vaccines and immune therapies.
- Subjects :
- Angiotensin-Converting Enzyme 2
Antibodies, Viral pharmacology
Antigenic Variation genetics
Carboxypeptidases immunology
Cell Line, Tumor
Disease Outbreaks
Epitopes
Humans
Membrane Glycoproteins immunology
Mutation, Missense
Peptidyl-Dipeptidase A
Receptors, Virus
Severe acute respiratory syndrome-related coronavirus genetics
Spike Glycoprotein, Coronavirus
Viral Envelope Proteins immunology
Antibodies, Viral immunology
Genetic Variation immunology
Membrane Glycoproteins genetics
Severe acute respiratory syndrome-related coronavirus immunology
Viral Envelope Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 102
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15642942
- Full Text :
- https://doi.org/10.1073/pnas.0409065102