Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.

PB1-F2 protein, expressed from an alternative reading frame of most influenza A virus (IAV) PB1 segments, may possess specific residues associated with enhanced inflammation (L62, R75, R79, and L82) and cytotoxicity (I68, L69, and V70). These residues were shown to increase the pathogenicity of prim...

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Main Authors: Irina V Alymova, Ian A York, Jonathan A McCullers
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4219726?pdf=render
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author Irina V Alymova
Ian A York
Jonathan A McCullers
author_facet Irina V Alymova
Ian A York
Jonathan A McCullers
author_sort Irina V Alymova
collection DOAJ
description PB1-F2 protein, expressed from an alternative reading frame of most influenza A virus (IAV) PB1 segments, may possess specific residues associated with enhanced inflammation (L62, R75, R79, and L82) and cytotoxicity (I68, L69, and V70). These residues were shown to increase the pathogenicity of primary viral and secondary bacterial infections in a mouse model. In contrast to human seasonal influenza strains, virulence-associated residues are present in PB1-F2 proteins from pandemic H1N1 1918, H2N2 1957, and H3N2 1968, and highly pathogenic H5N1 strains, suggesting their contribution to viruses' pathogenic phenotypes. Non-human influenza strains may act as donors of virulent PB1-F2 proteins. Previously, avian influenza strains were identified as a potential source of inflammatory, but not cytotoxic, PB1-F2 residues. Here, we analyze the frequency of virulence-associated residues in PB1-F2 sequences from IAVs circulating in mammalian species in close contact with humans: pigs, horses, and dogs. All four inflammatory residues were found in PB1-F2 proteins from these viruses. Among cytotoxic residues, I68 was the most common and was especially prevalent in equine and canine IAVs. Historically, PB1-F2 from equine (about 75%) and canine (about 20%) IAVs were most likely to have combinations of the highest numbers of residues associated with inflammation and cytotoxicity, compared to about 7% of swine IAVs. Our analyses show that, in addition to birds, pigs, horses, and dogs are potentially important sources of pathogenic PB1-F2 variants. There is a need for surveillance of IAVs with genetic markers of virulence that may be emerging from these reservoirs in order to improve pandemic preparedness and response.
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spelling doaj.art-9e4b902289c44f7b9cb7a3f03e9faf432022-12-21T23:28:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01911e11160310.1371/journal.pone.0111603Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.Irina V AlymovaIan A YorkJonathan A McCullersPB1-F2 protein, expressed from an alternative reading frame of most influenza A virus (IAV) PB1 segments, may possess specific residues associated with enhanced inflammation (L62, R75, R79, and L82) and cytotoxicity (I68, L69, and V70). These residues were shown to increase the pathogenicity of primary viral and secondary bacterial infections in a mouse model. In contrast to human seasonal influenza strains, virulence-associated residues are present in PB1-F2 proteins from pandemic H1N1 1918, H2N2 1957, and H3N2 1968, and highly pathogenic H5N1 strains, suggesting their contribution to viruses' pathogenic phenotypes. Non-human influenza strains may act as donors of virulent PB1-F2 proteins. Previously, avian influenza strains were identified as a potential source of inflammatory, but not cytotoxic, PB1-F2 residues. Here, we analyze the frequency of virulence-associated residues in PB1-F2 sequences from IAVs circulating in mammalian species in close contact with humans: pigs, horses, and dogs. All four inflammatory residues were found in PB1-F2 proteins from these viruses. Among cytotoxic residues, I68 was the most common and was especially prevalent in equine and canine IAVs. Historically, PB1-F2 from equine (about 75%) and canine (about 20%) IAVs were most likely to have combinations of the highest numbers of residues associated with inflammation and cytotoxicity, compared to about 7% of swine IAVs. Our analyses show that, in addition to birds, pigs, horses, and dogs are potentially important sources of pathogenic PB1-F2 variants. There is a need for surveillance of IAVs with genetic markers of virulence that may be emerging from these reservoirs in order to improve pandemic preparedness and response.http://europepmc.org/articles/PMC4219726?pdf=render
spellingShingle Irina V Alymova
Ian A York
Jonathan A McCullers
Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
PLoS ONE
title Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
title_full Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
title_fullStr Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
title_full_unstemmed Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
title_short Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers.
title_sort non avian animal reservoirs present a source of influenza a pb1 f2 proteins with novel virulence enhancing markers
url http://europepmc.org/articles/PMC4219726?pdf=render
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