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Updated: Aug 19, 2026

In Vitro Disassembly of Influenza A Virus Capsids by Gradient Centrifugation
Published on: March 27, 2016
The influenza A virus M2 cytoplasmic tail is required for infectious virus production and efficient genome packaging
Matthew F McCown1, Andrew Pekosz
1Department of Molecular Microbiology, Washington University School of Medicine, Campus Box 8230, 660 S. Euclid Ave., St. Louis, MO 63110-1093, USA.
Abstract:
The M2 integral membrane protein encoded by influenza A virus possesses an ion channel activity that is required for efficient virus entry into host cells. The role of the M2 protein cytoplasmic tail in virus replication was examined by generating influenza A viruses encoding M2 proteins with truncated C termini. Deletion of 28 amino acids (M2Stop70) resulted in a virus that produced fourfold-fewer particles but >1,000-fold-fewer infectious particles than wild-type virus. Expression of the full-length M2 protein in trans restored the replication of the M2 truncated virus. Although the M2Stop70 virus particles were similar to wild-type virus in morphology, the M2Stop70 virions contained reduced amounts of viral nucleoprotein and genomic RNA, indicating a defect in vRNP packaging. The data presented indicate the M2 cytoplasmic tail plays a role in infectious virus production by coordinating the efficient packaging of genome segments into influenza virus particles.
Insights
The influenza A virus M2 protein
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Influenza A virus M2 protein is an ion channel crucial for virus entry.
- The function of the M2 protein's cytoplasmic tail in viral replication is not fully understood.
Purpose of the Study:
- To investigate the role of the M2 protein cytoplasmic tail in influenza A virus replication.
- To determine how truncations in the M2 protein's C-terminus affect virus production and infectivity.
Main Methods:
- Generation of influenza A viruses with truncated M2 C-termini (M2Stop70).
- Analysis of viral particle production, infectivity, morphology, and content (nucleoprotein and genomic RNA).
- Complementation experiments expressing full-length M2 protein in trans.
Main Results:
- Truncation of the M2 cytoplasmic tail (M2Stop70) significantly reduced infectious virus production (>1,000-fold).
- M2Stop70 virus particles showed defects in packaging viral nucleoprotein and genomic RNA.
- Restoration of full-length M2 expression rescued viral replication.
Conclusions:
- The M2 protein cytoplasmic tail is essential for efficient infectious influenza A virus production.
- The M2 cytoplasmic tail plays a critical role in coordinating the packaging of viral genome segments into new virions.
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