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Viral Subversion of Autophagy

Viral Subversion of Autophagy

Based at Division of Virology, Addenbrooke’s Hospital
Supervised by Dr Rupert Beale (co-supervised by Dr Stephen Graham)

Background

Autophagy is a process used by the cell to generate nutrients in times of starvation. Autophagosomes are generated by engulfment of cytoplasmic contents in a double-membrane vesicle which then fuses with a lysosome. This process has been adapted for cellular self-defence: invading microbes can be dragged into autophagosomes. While successful viruses must avoid autophagocytic destruction, they can also benefit from the increased resources autophagy provides. This project aims to elucidate the molecular mechanisms by which viruses such as HSV and influenza modulate autophagy by identifying and characterising viral proteins that bind to LC3, a key autophagy component.

Recent Publications:

Guidelines for the use and interpretation of assays for monitoring autophagy. Klionsky DJ, Beale R and many others. Autophagy, in press.

A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.

Beale R, Wise H, Stuart A, Ravenhill BJ, Digard P, Randow F.

Cell Host Microbe. 2014 Feb 12;15(2):239-47. doi: 10.1016/j.chom.2014.01.006.

Recruitment of VPS33A to HOPS by VPS16 Is Required for Lysosome Fusion with Endosomes and Autophagosomes.

Wartosch L, Günesdogan U, Graham SC, Luzio JP.

Traffic. 2015 Jul;16(7):727-42. doi: 10.1111/tra.12283. Epub 2015 Apr 30.

 

Vaccinia virus protein A49 is an unexpected member of the B-cell Lymphoma (Bcl)-2 protein family.

Neidel S, Maluquer de Motes C, Mansur DS, Strnadova P, Smith GL, Graham SC.

J Biol Chem. 2015 Mar 6;290(10):5991-6002. doi: 10.1074/jbc.M114.624650. Epub 2015 Jan 20.

 

Clathrin adaptors. AP2 controls clathrin polymerization with a membrane-activated switch.

Kelly BT, Graham SC, Liska N, Dannhauser PN, Höning S, Ungewickell EJ, Owen DJ.

Science. 2014 Jul 25;345(6195):459-63. doi: 10.1126/science.1254836.

 

More information on the supervisor’s research can be found on their research group website

http://www.path.cam.ac.uk/directory/rupert-beale

http://www.path.cam.ac.uk/directory/stephen-graham