ArticleJournal of virology2018
Ubiquitination of the Cytoplasmic Domain of Influenza A Virus M2 Protein Is Crucial for Production of Infectious Virus Particles.
Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Evolutionary Rate Variation at Predicted PTM Sites Reveals Localized Host-Associated Patterns in Influenza A Virus.Genome biology and evolution · 2026Article
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- Regulation of HPV-16 infection by ubiquitination of the L1 major capsid protein.Journal of virology · 2026Article
- Mass Spectrometry-Based Proteomic Analysis of Porcine Reproductive and Respiratory Syndrome Virus NSP9 Protein with Host Proteins.Animals : an open access journal from MDPI · 2025Article
- Membrane-Targeting Antivirals.International journal of molecular sciences · 2025Review
- New characteristics of cancer immunotherapy: trends in viral tumor immunotherapy with influenza virus-based approaches.Journal of Zhejiang University. Science. B · 2025Review
- An evolutionarily conserved ubiquitin ligase drives infection and transmission of flaviviruses.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TRAF6 autophagic degradation byAutophagy · 2022Article
- A Glu-Glu-Tyr Sequence in the Cytoplasmic Tail of the M2 Protein Renders Influenza A Virus Susceptible to Restriction of the Hemagglutinin-M2 Association in Primary Human Macrophages.Journal of virology · 2022Article
- Transcriptome Analysis of Peripheral Blood Mononuclear Cells Response in Patients with Severe COVID-19 Reveals Crucial Genes Regulating Protein Ubiquitination.Medical science monitor : international medical journal of experimental and clinical research · 2022Article
- The Roles of Ubiquitination in Pathogenesis of Influenza Virus Infection.International journal of molecular sciences · 2022Review
- Protein Palmitoylation Modification During Viral Infection and Detection Methods of Palmitoylated Proteins.Frontiers in cellular and infection microbiology · 2022Review
- Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.Frontiers in immunology · 2022Review
- A Review and Meta-Analysis of Influenza Interactome Studies.Frontiers in microbiology · 2022Review
- Influenza A M2 recruits M1 to the plasma membrane: A fluorescence fluctuation microscopy study.Biophysical journal · 2021Article
- G1-like PB2 gene improves virus replication and competitive advantage of H9N2 virus.Virus genes · 2021Article
- Review
- MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes.Nature communications · 2021Article
- Review
- Packaging signal of influenza A virus.Virology journal · 2021Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Virus replication is mediated by interactions between the virus and host. Here, we demonstrate that influenza A virus membrane protein 2 (M2) can be ubiquitinated. The lysine residue at position 78, which is located in the cytoplasmic domain of M2, is essential for M2 ubiquitination. An M2-K78R (Lys78→Arg78) mutant, which produces ubiquitination-deficient M2, showed a severe defect in the production of infectious virus particles. M2-K78R mutant progeny contained more hemagglutinin (HA) proteins, less viral RNAs, and less internal viral proteins, including M1 and NP, than the wild-type virus. Furthermore, most of the M2-K78R mutant viral particles lacked viral ribonucleoproteins upon examination by electron microscopy and exhibited slightly lower densities. We also found that mutant M2 colocalized with the M1 protein to a lesser extent than for the wild-type virus. These findings may account for the reduced incorporation of viral ribonucleoprotein into virions. By blocking the second round of virus infection, we showed that the M2 ubiquitination-defective mutant exhibited normal levels of virus replication during the first round of infection, thereby proving that M2 ubiquitination is involved in the virus production step. Finally, we found that the M2-K78R mutant virus induced autophagy and apoptosis earlier than did the wild-type virus. Collectively, these results suggest that M2 ubiquitination plays an important role in infectious virus production by coordinating the efficient packaging of the viral genome into virus particles and the timing of virus-induced cell death.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.