Matrix Protein 1 of Influenza Virus: Structure, Functions, and Role in the Viral Life Cycle

Matrix protein 1 (M1) is the most abundant protein in the influenza virion. It plays essential roles during the entire viral replication cycle. These roles include virus entry, uncoating, assembly, and budding.
Matrix protein 1 consists of 252 amino acids. The protein is organized into three domains. Each domain contains tightly packed alpha-helical bundles, connected by short linker regions. This structure enables Matrix protein 1 to form multimers and interact with other viral components.

The Influenza A M1 Peptide Pool covers the complete Matrix Protein 1.

1. How does Matrix protein 1 interact with Viral Components?

Matrix protein 1 interacts with several key structures of the virus:

1.1. Lipid Envelope

In the virion, Matrix protein 1 forms a continuous protein layer on the inner surface of the viral lipid envelope. This protein layer provides mechanical stability to the virion and influences the shape of the virus particle. Influenza virions can be either spherical or filamentous. Clinical isolates often show a high proportion of filamentous virions. [1] These filaments may help spread the virus to neighboring cells. In contrast, spherical particles are more common after repeated passage in eggs or cell culture. These are thought to be more efficient for aerosol transmission between hosts.

Responsible for binding to the lipid envelope is the amino acid sequence 1-164 of Matrix Protein 1. peptides&elephants provides the following peptides from the membrane-binding sequence:

Influenza A M1 13-21 (HLA-A*11:01)(HLA-A*03:01)(HLA-A*31:01)(HLA-A*68:01) with the amino acid sequence SIIPSGPLK
Influenza A M1 58-66 (HLA-A*02:01) with the amino acid sequence GILGFVFTL
Influenza A M1 59-68 (HLA-A*02:01) with the amino acid sequence ILGFVFTLTV
Influenza A M1 125–132 (HLA-B27) (HLA-B35) with the amino acid sequence ASCMGLIY

1.2. Viral Ribonucleoproteins (vRNPs)

The continuous layer of Matrix protein 1 on the inner side of the viral lipid bilayer anchors the viral ribonucleoproteins (vRNPs). [2] The vRNPs comprise the viral RNA, the associated nucleoprotein (NP), and a polymerase complex, which together form a functional unit. The binding of Matrix protein 1 appears to suppress transcription of the viral genome until Matrix protein 1 is removed.

Responsible for binding to vRNPs is the amino acid sequence 165-252 of Matrix Protein 1. peptides&elephants provides the epitope Influenza A M1 178-187 (HLA-A*11:01) with the amino acid sequence RMVLASTTAK.

1.3. Matrix protein 2 (M2) Ion Channel Protein

Matrix protein 1 is linked to the function of the Matrix protein 2 (M2) proton channel. M2 acidifies the virion interior after it was internalized by endocytosis of the host cell. This triggers Matrix protein 1 to dissociate from vRNPs.

1.4. Surface Glycoproteins Hemagglutinin (HA) and Neuraminidase (NA)

Matrix protein 1 interacts with the cytoplasmic tails of Hemagglutinin and Neuraminidase. This interaction helps recruit Matrix protein 1 into lipid rafts, which are specialized membrane domains.

1.5. Nuclear Export Protein (NEP)

Nuclear Export Protein binds to the Matrix protein 1–vRNP complex. In polarized epithelial cells, this promotes nuclear export of the complex toward the apical plasma membrane, where virus assembly occurs.

2. Function of Matrix protein 1 in the Viral Life Cycle

2.1. Viral Entry and Uncoating

After viral entry by endocytosis, the low pH inside the endosome activates the M2 ion channel. Protons enter the virion and lower the pH inside. This causes Matrix protein 1 to dissociate from vRNPs. The released vRNPs are then transported to the nucleus for transcription and replication.

2.2. Regulation of Transcription

The dissociation of Matrix protein 1 is necessary to initiate viral RNA synthesis. NEP-mediated export of Matrix protein 1–vRNP complexes ensures proper timing of replication and assembly.

2.3. Virus Assembly and Budding

Matrix protein 1 plays a central role in assembling new virus particles. During budding, Matrix protein 1 forms a multimeric network beneath the viral envelope. This structure is stabilized by interactions with Hemagglutinin (HA), Neuraminidase (NA), and the lipid bilayer. Matrix protein 1 ensures the proper incorporation of vRNPs and surface proteins into new virions.

3. Conclusion

Matrix protein 1 is essential for influenza virus replication. It provides structural support, regulates genome release, controls transcription, and enables efficient assembly. Due to its central role and high abundance, Matrix protein 1 is a promising target for antiviral strategies and drug development.

Literature

Dadonaite, Bernadeta et al. “Filamentous influenza viruses.” The Journal of general virology vol. 97,8 (2016): 1755-1764. doi:10.1099/jgv.0.000535
Eisfeld, Amie J et al. “At the centre: influenza A virus ribonucleoproteins.” Nature reviews. Microbiology vol. 13,1 (2015): 28-41. doi:10.1038/nrmicro3367