Influenza virus adaptation PB2-627K modulates nucleocapsid inhibition by the pathogen sensor RIG-I

Michaela Weber1, Hanna Sediri1, Ulrike Felgenhauer1

  • 1Institute for Virology, Philipps-University Marburg, D-35043 Marburg, Germany.

Cell Host & Microbe
|February 24, 2015
PubMed

Insights

The RNA helicase RIG-I directly restricts avian influenza A virus (FLUAV) by recognizing viral nucleocapsids. Specific viral polymerase changes enhance RIG-I sensing, inhibiting infection independently of antiviral signaling.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Cytoplasmic RNA helicase RIG-I is crucial for innate immune sensing of RNA viruses.
  • Influenza A virus (FLUAV) genome packaging by nucleoprotein and RNA polymerase can impede RIG-I recognition.

Purpose of the Study:

  • To investigate how RIG-I senses FLUAV nucleocapsids.
  • To determine the role of viral polymerase subunit PB2 polymorphisms in RIG-I recognition and viral infectivity.

Main Methods:

  • Analysis of RIG-I recognition of FLUAV nucleocapsids with varying PB2 polymerase subunit.
  • Assessment of viral infectivity in RIG-I-deficient cells.
  • Correlation of RIG-I sensing with nucleoprotein binding affinity and nucleocapsid stability.

Main Results:

  • RIG-I recognizes 5'-triphosphorylated dsRNA on FLUAV nucleocapsids.
  • Avian FLUAV nucleocapsids with PB2-627E are more readily recognized by RIG-I than mammalian-adapted PB2-627K.
  • RIG-I deficiency partially restores infectivity of PB2-627E viruses in mammalian cells.
  • Heightened RIG-I sensing of PB2-627E correlates with reduced PB2-nucleoprotein affinity and increased nucleocapsid instability.
  • RIG-I binding to nucleocapsids inhibits infection independently of downstream antiviral signaling.

Conclusions:

  • RIG-I acts as a direct restriction factor against avian FLUAV.
  • Nucleocapsid disruption is a potential antiviral strategy against influenza viruses.

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