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Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.

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.

journal_name

Virology

journal_title

Virology

authors

Maines TR,Chen LM,Van Hoeven N,Tumpey TM,Blixt O,Belser JA,Gustin KM,Pearce MB,Pappas C,Stevens J,Cox NJ,Paulson JC,Raman R,Sasisekharan R,Katz JM,Donis RO

doi

10.1016/j.virol.2011.02.015

subject

Has Abstract

pub_date

2011-04-25 00:00:00

pages

139-47

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(11)00076-6

journal_volume

413

pub_type

杂志文章

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