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Updated: Jul 8, 2025

Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells
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Affinity Purification of Influenza Virus Ribonucleoprotein Complexes from the Chromatin of Infected Cells

Published on: June 3, 2012

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N-terminal acetylation controls multiple functional aspects of the influenza A virus ribonuclease PA-X

Raecliffe E Daly1,2, Idalia Myasnikov2,3, Marta Maria Gaglia2

  • 1Program in Cellular, Molecular and Developmental Biology, Tufts University Graduate School of Biomedical Sciences, Boston, MA, 02111, United States.

Biorxiv : the Preprint Server for Biology
|December 11, 2023
PubMed

Insights

Influenza A virus PA-X protein uses N-terminal acetylation for host shutoff. Acetylation of the initiator methionine is crucial for PA-X activity and nuclear localization, revealing a complex regulatory mechanism.

Area of Science:

  • Virology
  • Molecular Biology
  • Host-Pathogen Interactions

Background:

  • Influenza A virus employs a

Purpose of the Study:

  • To elucidate the molecular mechanisms by which N-terminal acetylation of the influenza A virus PA-X protein regulates its host shutoff activity.
  • To investigate the distinct roles of N-terminal acetylation at different positions on PA-X in mediating its functions.

Main Methods:

  • Site-directed mutagenesis to alter N-terminal acetylation sites on PA-X.
  • Analysis of PA-X localization using microscopy.
  • Assessment of host shutoff activity in cells expressing modified PA-X.
  • Investigation of interactions between PA-X and influenza protein NS1.

Main Results:

  • N-terminal acetylation of PA-X at either the initiator methionine or the second amino acid promotes nuclear localization.
  • Acetylation of the initiator methionine is essential for PA-X host shutoff activity in ectopically expressed systems.
  • During infection, N-terminal acetylation at any position confers host shutoff activity, partly through interaction with NS1.
  • PA-X N-terminal acetylation plays a multifaceted role in regulating viral activity and host immune response.

Conclusions:

  • N-terminal acetylation of influenza A virus PA-X is a critical regulatory mechanism with distinct functions depending on the acetylation site.
  • The initiator methionine acetylation is specifically required for PA-X host shutoff function, while other sites facilitate nuclear import.
  • Functional interaction with NS1 contributes to PA-X activity during infection, highlighting a coordinated viral strategy.

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