Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion
Citation
Ivanovic, Tijana, and Stephen C Harrison. 2015. “Distinct functional determinants of influenza hemagglutinin-mediated membrane fusion.” eLife 4 (1): e11009. doi:10.7554/eLife.11009. http://dx.doi.org/10.7554/eLife.11009.Abstract
Membrane fusion is the critical step for infectious cell penetration by enveloped viruses. We have previously used single-virion measurements of fusion kinetics to study the molecular mechanism of influenza-virus envelope fusion. Published data on fusion inhibition by antibodies to the 'stem' of influenza virus hemagglutinin (HA) now allow us to incorporate into simulations the provision that some HAs are inactive. We find that more than half of the HAs are unproductive even for virions with no bound antibodies, but that the overall mechanism is extremely robust. Determining the fraction of competent HAs allows us to determine their rates of target-membrane engagement. Comparison of simulations with data from H3N2 and H1N1 viruses reveals three independent functional variables of HA-mediated membrane fusion closely linked to neutralization susceptibility. Evidence for compensatory changes in the evolved mechanism sets the stage for studies aiming to define the molecular constraints on HA evolvability. DOI: http://dx.doi.org/10.7554/eLife.11009.001Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4755761/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:25658463
Collections
- FAS Scholarly Articles [18292]
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)