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Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells.
Open accessAbstract
Cleavage of the hemagglutinin (HA) in tissue culture systems has been correlated with virulence of avian influenza viruses. To examine the structural requirements for cleavage of the HA, the HA gene from a virulent H5 influenza virus was expressed in mammalian cells (CV-1), and the cleavage site of the HA was explored by using site-specific mutagenesis. The expressed HA protein exhibited normal cleavage, transport to the cell membrane, and ability to adsorb and to fuse erythrocytes at pH 5. Site-specific mutagenesis of the HA directly established that (i) most of the basic amino acids at this site are critical for cleavage activation; (ii) besides the connecting peptide sequence, at least one other structural feature of the HA is required for enzyme recognition; and (iii) the length of the connecting peptide can abrogate the structural feature(s).
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Cited by
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Itoh, Y., Shinya, K., Kiso, M., Watanabe, T., Sakoda, Y., Hatta, M., Muramoto, Y., Tamura, D., Sakai-Tagawa, Y., Noda, T., et al. (2009) · Nature · doi:10.1038/nature08260 · Cited by 1,073
Self-citationInfluenza: lessons from past pandemics, warnings from current incidents
Horimoto, T., & Kawaoka, Y. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1208 · Cited by 696
Self-citationRole of hemagglutinin cleavage for the pathogenicity of influenza virus.
Steinhauer, D. A. (1999) · Virology · doi:10.1006/viro.1999.9716 · Cited by 663
Pandemic Threat Posed by Avian Influenza A Viruses
Horimoto, T., & Kawaoka, Y. (2001) · Clinical Microbiology Reviews · doi:10.1128/cmr.14.1.129-149.2001 · Cited by 542
Self-citationThe 2009 A (H1N1) influenza virus pandemic: A review
Girard, M. P., Tam, J. S., Assossou, O. M., & Kieny, M. P. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.05.031 · Cited by 488
Metadata
- Authors
- Kawaoka, Y., & Webster, R. G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1988-01
- Volume
- 85
- Issue
- 2
- Pages
- 324-328
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1995189663
- Cited by
- 250
- References
- 0
- FWCI
- 9.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Kawaoka, Y., & Webster, R. G. (1988). Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.85.2.324
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