tetano
Editor, Senior Moderator
J Virol. 2013 Sep 11. [Epub ahead of print]
A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein.
Hooper KA, Bloom JD.
Source
Molecular and Cellular Biology Program, University of Washington, Seattle, WA.
Abstract
In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, while neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. Here we report the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red-blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that at least in tissue culture, influenza's receptor-binding activity can be entirely shifted from HA to NA.
PMID:
24027333
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027333
A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding protein.
Hooper KA, Bloom JD.
Source
Molecular and Cellular Biology Program, University of Washington, Seattle, WA.
Abstract
In the vast majority of influenza A viruses characterized to date, hemagglutinin (HA) is the receptor-binding and fusion protein, while neuraminidase (NA) is a receptor-cleaving protein that facilitates viral release but is expendable for entry. However, the NAs of some recent human H3N2 isolates have acquired receptor-binding activity via the mutation D151G, although these isolates also appear to retain the ability to bind receptors via HA. Here we report the laboratory generation of a mutation (G147R) that enables an N1 NA to completely co-opt the receptor-binding function normally performed by HA. Viruses with this mutant NA grow to high titers even in the presence of extensive mutations to conserved residues in HA's receptor-binding pocket. When the receptor-binding NA is paired with this binding-deficient HA, viral infectivity and red-blood cell agglutination are blocked by NA inhibitors. Furthermore, virus-like particles expressing only the receptor-binding NA agglutinate red blood cells in an NA-dependent manner. Although the G147R NA receptor-binding mutant virus that we characterize is a laboratory creation, this same mutation is found in several natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that at least in tissue culture, influenza's receptor-binding activity can be entirely shifted from HA to NA.
PMID:
24027333
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24027333