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The role of the cytoplasmic tail of the influenza virus M2 protein in viral morphology and replication

Badham, Matthew (2018) The role of the cytoplasmic tail of the influenza virus M2 protein in viral morphology and replication. Doctor of Philosophy (PhD) thesis, University of Kent,.

Abstract

The influenza A virus is the causative agent of influenza virus disease - commonly known as 'the flu'. Considerable numbers of people are infected seasonally, with most illness resolving quickly. The social and economic impact can be severe, and presents a significant burden for healthcare systems.

M2 is also known to interact with many of the other viral and cellular proteins during all stages of viral infection. It binds to both the matrix protein 1, M1, and possibly interacts with the nucleoprotein, NP, as well as interacting with cellular factors such as Annexin A6, and cholesterol. Biophysically, M2 is crucial during viral budding in that it provides the force necessary to induce negative gaussian membrane curvature which enables 'pinching off' of new virions.

Here we show that the cytoplasmic tail (CT) of M2 is able to interact with many cellular proteins and processes, such as autophagy through LC3 binding, the cellular SUMO system through a SUMO interacting motif, SIM, and the cellular intermediate filament Vimentin. We have used a myriad of techniques in an attempt to elucidate and characterise these interactions of the M2 CT, and how mutations in the M2 CT may ultimately affect viral morphology. Further understanding of viral morphology being affected by other viral proteins and has been investigated through the study of live attenuated influenza viruses (LAIVs) used in seasonal vaccinations. Through this, a medically applicable outcome of influenza morphology is also presented for future investigation.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Rossman, Jeremy
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculties > Sciences > School of Biosciences
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 16 Dec 2019 10:10 UTC
Last Modified: 18 Dec 2019 00:00 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/79310 (The current URI for this page, for reference purposes)
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