Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.
Summary of "Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses."
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.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA.
This article was published in the following journal.
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21397290
- DOI: http://dx.doi.org/10.1016/j.virol.2011.02.015
Medical and Biotech [MESH] Definitions
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A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
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