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Rank orders of mammalian pathogenicity-related PB2 mutations of avian influenza A viruses

Chung-Young Lee1, Se-Hee An1, Jun-Gu Choi2

  • 1Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, 08826, Seoul, Republic of Korea.

Scientific Reports
|March 27, 2020
PubMed

Insights

This study ranks mutations in avian influenza A virus (IAV) PB2 genes, revealing that accumulating mutations enhance mammalian pathogenicity. Understanding these mutation orders is key to predicting IAV risks.

Area of Science:

  • Virology
  • Molecular Biology
  • Evolutionary Biology

Background:

  • The PB2 gene is crucial for avian influenza A viruses (IAVs) to adapt to mammals.
  • Mammalian pathogenicity-related mutations (MPMs) in PB2 have been identified, but their comparative effects and evolutionary steps remain unclear.

Purpose of the Study:

  • To collectively compare the effects of individual and combined MPMs on viral fitness.
  • To determine the rank order of MPMs during mammalian adaptation using a prototypic PB2 gene.
  • To assess the role of early mutations in the acquisition of subsequent mutations and overall pathogenicity.

Main Methods:

  • Comparative analysis of single and multiple MPMs within a prototypic PB2 gene.
  • Assessment of viral fitness and pathogenicity associated with different MPM combinations.
  • Determination of mutation rank orders during avian influenza virus adaptation.

Main Results:

  • A clear rank order of MPMs was established, demonstrating their cumulative effect on viral fitness.
  • Early acquired mutations were found to influence the function and potency of subsequent mutations.
  • Increased accumulation of MPMs directly correlated with higher mammalian pathogenicity.

Conclusions:

  • The rank order of MPMs and the use of a prototypic PB2 gene can predict the risks associated with avian and mammalian IAVs.
  • Understanding mutation accumulation is vital for assessing the pandemic potential of influenza viruses.
  • Early mutations play a significant role in the evolutionary trajectory of IAVs towards mammalian adaptation.

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