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PloS one2014; 9(11); e111603; doi: 10.1371/journal.pone.0111603

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

Abstract: 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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Publication Date: 2014-11-04 PubMed ID: 25368997PubMed Central: PMC4219726DOI: 10.1371/journal.pone.0111603Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the role of certain proteins in the influenza A virus (IAV), particularly PB1-F2 proteins, in increasing disease severity. It suggests that PB1-F2 proteins found in non-human influenza strains may contribute to virus pathogenicity, with a focus on those circulating in pigs, horses, and dogs.

Understanding the PB1-F2 Protein

  • The PB1-F2 protein is expressed from an alternative reading frame of most IAV PB1 segments. Certain residues of this protein – L62, R75, R79, L82, I68, L69, and V70 – have been associated with enhanced inflammation and cytotoxicity.
  • These residues are thought to make primary viral and secondary bacterial infections more severe in a mouse model. This suggests that they could play a role in increasing the pathogenicity or disease-causing ability of the viruses.

Virulence-Associated Residues

  • Different influenza strains have varying levels of these virulence-associated residues. While they’re absent in human seasonal influenza strains, they’re present in PB1-F2 proteins from historical pandemic strains like H1N1 (1918), H2N2 (1957), H3N2 (1968), and the highly pathogenic H5N1 strain. This presence suggests that these residues could contribute to the pathogenic phenotypes, or disease-causing characteristics, of these viruses.
  • The study posits that non-human influenza strains could act as sources of these virulent PB1-F2 proteins. Formerly, avian influenza strains were recognized as possible sources of inflammatory, but not cytotoxic, PB1-F2 residues.

Analyzing Virulence-Associated Residues in Different Animal Species

  • The research looked at the frequency of virulence-associated residues in PB1-F2 sequences from IAVs circulating in pigs, horses, and dogs – mammals often in close contact with humans.
  • All four inflammatory residues were found in the PB1-F2 proteins from these animals’ viruses. Among the cytotoxic residues, I68 was the commonest, particularly in equine and canine IAVs.
  • Historically, PB1-F2 proteins from equine (about 75%) and canine (about 20%) IAVs were more likely to have combinations of the highest numbers of inflammation- and cytotoxicity-associated residues compared to about 7% of swine IAVs.

Implications and Recommendations

  • The researchers conclude that, in addition to birds, pigs, horses, and dogs could be important sources of pathogenic PB1-F2 variants.
  • A vigilant surveillance of IAVs with virulence genetic markers potentially emerging from these reservoirs is crucial to enhance pandemic preparedness and response.

Cite This Article

APA
Alymova IV, York IA, McCullers JA. (2014). Non-avian animal reservoirs present a source of influenza A PB1-F2 proteins with novel virulence-enhancing markers. PLoS One, 9(11), e111603. https://doi.org/10.1371/journal.pone.0111603

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 11
Pages: e111603
PII: e111603

Researcher Affiliations

Alymova, Irina V
  • Influenza Division, National Center for Immunization & Respiratory Diseases, Centers for Disease Control & Prevention, Atlanta, Georgia, United States of America; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
York, Ian A
  • Influenza Division, National Center for Immunization & Respiratory Diseases, Centers for Disease Control & Prevention, Atlanta, Georgia, United States of America.
McCullers, Jonathan A
  • Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.

MeSH Terms

  • Animals
  • Dogs / blood
  • Dogs / virology
  • Horses / blood
  • Horses / virology
  • Humans
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Influenza A virus / isolation & purification
  • Influenza A virus / pathogenicity
  • Influenza, Human / transmission
  • Influenza, Human / virology
  • Orthomyxoviridae Infections / blood
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Phylogeny
  • Swine / blood
  • Swine / virology
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / immunology

Conflict of Interest Statement

The authors of this manuscript, Drs. Irina Alymova and Jon McCullers, have the following competing interests: patent application SJ0060US “Method and kit for detecting virulent strains of influenza virus”. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials.

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Citations

This article has been cited 8 times.
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