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The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation

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Abstract

The matrix protein 2 (M2) is a spliced product of segment 7 genome of influenza A virus. Previous studies indicate its role in uncoating of the viral ribonucleoprotein complex during viral entry and in membrane scission while budding. Despite its crucial role in the viral life cycle, little is known about its subcellular distribution and dynamics. In this study, we have shown that the M2 protein is translocated from the membrane to the cytoplasm by a retrograde route via endosomes and the Golgi network. It utilizes retromer cargo while moving from the endosome to the trans-Golgi network and prevents endosome fusion with the lysosome. Further, M2 interacts with the endoplasmic-reticulum-resident AAA-ATPase p97 for its release into the cytoplasm. Our study also revealed that the M2 protein in the cellular milieu does not undergo ubiquitin-mediated proteasomal degradation. The migration of M2 through this pathway inside the infected cell suggests possible new roles that the M2 protein may have in the host cytoplasm, apart from its previously described functions.

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Acknowledgements

We thank Dr. T. A. Rapoport and Dr. S. Jameel for providing us the plasmid constructs. Our special thanks also go to R. Kumar and P. Kumar for assistance in virus infection, confocal microscopy and cell culture experiments.

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Authors and Affiliations

  1. Virology Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

    Sanchari Bhowmick, Chandrani Chakravarty & Sunil K. Lal

  2. Department of Biomedical Science, Bharathidasan University, Trichy, India

    Chandrani Chakravarty & Shanmugaapriya Sellathamby

  3. School of Science, Monash University, 47500, Bandar Sunway, Malaysia

    Sunil K. Lal

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  1. Sanchari Bhowmick
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  2. Chandrani Chakravarty
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  3. Shanmugaapriya Sellathamby
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  4. Sunil K. Lal
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Correspondence to Sunil K. Lal.

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S. Bhowmick: Deceased.

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Bhowmick, S., Chakravarty, C., Sellathamby, S. et al. The influenza A virus matrix protein 2 undergoes retrograde transport from the endoplasmic reticulum into the cytoplasm and bypasses cytoplasmic proteasomal degradation. Arch Virol 162, 919–929 (2017). https://doi.org/10.1007/s00705-016-3153-8

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  • DOI: https://doi.org/10.1007/s00705-016-3153-8

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