Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses
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Maines-2011-Effect of receptor b.pdf
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Author(s)
Maines, Taronna R.
Chen, Li-Mei
Van Hoeven, Neal
Tumpey, Terrence M.
Blixt, Ola
Belser, Jessica A.
Gustin, Kortney M.
Pearce, Melissa B.
Pappas, Claudia
Stevens, James
Date Issued
March 2011
Journal
Virology
Publisher
Elsevier
Citation
Maines, Taronna R., Li-Mei Chen, Neal Van Hoeven, Terrence M. Tumpey, Ola Blixt, Jessica A. Belser, Kortney M. Gustin, et al. “Effect of Receptor Binding Domain Mutations on Receptor Binding and Transmissibility of Avian Influenza H5N1 Viruses.” Virology 413, no. 1 (April 2011): 139–147. © 2011 Elsevier Inc.
Version
Final published version
Abstract
Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. School of Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.virol.2011.02.015
