The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels

Robert A Lamb1

  • 1Department of Molecular Biosciences, Howard Hughes Medical Institute, Northwestern University, Evanston, Illinois 60208-3500, USA.

Insights

Influenza A and B viruses utilize M2 proteins as proton channels. These channels are crucial for virus replication, assembly, and budding, and are targeted by antiviral drugs.

Area of Science:

  • Virology
  • Structural Biology
  • Membrane Protein Function

Background:

  • Influenza A virus M2 (AM2) protein functions as a proton-selective ion channel (viroporin).
  • AM2 protein features extracellular residues, a transmembrane domain, and a cytoplasmic tail, forming a four-helix bundle.
  • AM2 channel activity is pH-dependent, with His37 as the sensor and Trp41 as the gate, and is inhibited by amantadine hydrochloride.

Purpose of the Study:

  • To elucidate the structural and functional characteristics of influenza A virus M2 (AM2) and influenza B virus BM2 proteins.
  • To investigate the conserved functions of AM2 and BM2 proteins in viral life cycles.
  • To understand the role of AM2 in virus assembly and independence from the ESCRT complex.

Main Methods:

  • Structural analysis of the AM2 protein's four-helix bundle.
  • Functional characterization of proton channel activity and pH gating.
  • Investigation of AM2's role in virus budding and ESCRT-independent scission.

Main Results:

  • AM2 forms a proton channel with high selectivity over Na+ ions.
  • His37 and Trp41 residues are critical for pH sensing and channel gating, respectively.
  • AM2 facilitates virus budding and enables ESCRT-independent virus release.

Conclusions:

  • AM2 and BM2 proteins share functional similarities, including proton sensing and gating mechanisms.
  • AM2 protein plays a vital role in influenza virus assembly, budding, and replication.
  • Targeting the M2 channel with drugs like amantadine hydrochloride is a viable antiviral strategy.

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