| Literature DB >> 24725402 |
Martin Linster1, Sander van Boheemen1, Miranda de Graaf1, Eefje J A Schrauwen1, Pascal Lexmond1, Benjamin Mänz1, Theo M Bestebroer1, Jan Baumann2, Debby van Riel1, Guus F Rimmelzwaan1, Albert D M E Osterhaus1, Mikhail Matrosovich2, Ron A M Fouchier3, Sander Herfst1.
Abstract
Recently, A/H5N1 influenza viruses were shown to acquire airborne transmissibility between ferrets upon targeted mutagenesis and virus passage. The critical genetic changes in airborne A/Indonesia/5/05 were not yet identified. Here, five substitutions proved to be sufficient to determine this airborne transmission phenotype. Substitutions in PB1 and PB2 collectively caused enhanced transcription and virus replication. One substitution increased HA thermostability and lowered the pH of membrane fusion. Two substitutions independently changed HA binding preference from α2,3-linked to α2,6-linked sialic acid receptors. The loss of a glycosylation site in HA enhanced overall binding to receptors. The acquired substitutions emerged early during ferret passage as minor variants and became dominant rapidly. Identification of substitutions that are essential for airborne transmission of avian influenza viruses between ferrets and their associated phenotypes advances our fundamental understanding of virus transmission and will increase the value of future surveillance programs and public health risk assessments.Entities:
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Year: 2014 PMID： 24725402 PMCID： PMC4003409 DOI： 10.1016/j.cell.2014.02.040
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582