The DOI matches its Crossref record.
Permissive Secondary Mutations Enable the Evolution of Influenza Oseltamivir Resistance
Open accessAbstract
Influenza Escape Tricks: Tamiflu, or oseltamivir, has been extensively stockpiled by several governments in anticipation of a dangerous influenza pandemic. So far, its large-scale use has not been required, but, despite this, resistance has emerged in seasonal strains mediated by a single point mutation of histidine to tyrosine in the 274 residue (H274Y) of neuraminidase. When the resistant virus was first discovered in 1998, it grew poorly, but by 2008 the virus was reinvigorated and the mutation had spread worldwide in seasonal influenza. So what happened that improved viral fitness so radically? Bloom et al. (p. 1272 ; see the Perspective by Holmes ) show that the H274Y mutation hinders the folding of the neuraminidase enzyme. In the more vigorous recent oseltamivir-resistant isolates, other mutations compensate for the deleterious effect of H274Y and restore fitness to the virus.
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Cited by
Starr, T. N., Greaney, A. J., Hilton, S. K., Ellis, D., Crawford, K. H. D., Dingens, A. S., Navarro, M. J., Bowen, J. E., Tortorici, M. A., Walls, A. C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.012 · Cited by 1,956
Self-citationProspective mapping of viral mutations that escape antibodies used to treat COVID-19
Starr, T. N., Greaney, A. J., Addetia, A., Hannon, W. W., Choudhary, M. C., Dingens, A. S., Li, J. Z., & Bloom, J. D. (2021) · Science · doi:10.1126/science.abf9302 · Cited by 743
“A caveat is that over longer evolutionary timeframes, the space of tolerated mutations could shift due to epistatic interactions, as has been observed in viral immune and drug escape ( 19 – 21 ).”
BackgroundSelf-citationRules of engagement: molecular insights from host–virus arms races
Daugherty, M. D., & Malik, H. S. (2012) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155522 · Cited by 515
The mechanism of resistance to favipiravir in influenza
Goldhill, D. H., te Velthuis, A. J. W., Fletcher, R. A., Langat, P., Zambon, M., Lackenby, A., & Barclay, W. S. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811345115 · Cited by 298
The Causes and Consequences of Genetic Interactions (Epistasis)
Domingo, J., Baeza-Centurion, P., & Lehner, B. (2019) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-083118-014857 · Cited by 242
Metadata
- Authors
- Bloom, J. D., Gong, L. I., & Baltimore, D.
- Venue
- Science
- Published
- 2010-06-04
- Volume
- 328
- Issue
- 5983
- Pages
- 1272-1275
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2046094044
- Cited by
- 649
- References
- 0
- FWCI
- 37.53
- Type
- journal article
- Language
- en
- Open access
- green
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