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Title: Vaccinia virus as a tool to study novel mechanisms of host cell contraction and blebbing
Author: Durkin, C. H.
ISNI:       0000 0004 2739 3510
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2012
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Vaccinia is a widely studied member of the poxvirus family. Throughout its life cycle, vaccinia manipulates cellular processes of the host to aid its replication and spread. Early in infection vaccinia stimulates transient host cell contraction, associated with dynamic plasma membrane blebbing and migration, reminiscent of the RhoA-ROCK regulated amoeboid migration of cancer cells. Cell contraction required the expression of early vaccinia genes whilst subsequent re-spreading required late vaccinia genes. Using a virus that does not express the vaccinia protein F11, I showed that F11 was required for virus infection to stimulate contraction. However, using a highly attenuated vaccinia strain rescued with wild type F11, MVA-F11, I found that cell contraction additionally required other vaccinia proteins. Live cell imaging of F11-GFP revealed that F11 is recruited to the plasma membrane during blebbing, further supporting a role for F11 in regulating these membrane events. Despite previous evidence from this laboratory showing F11 interacts with RhoA, I found that cell contraction was independent of RhoA. Instead vaccinia induced contraction required RhoC to ROCK signalling. Furthermore, using a small siRNA screen of several Rho GTPases, I discovered that RhoD negatively regulates vaccinia-induced contraction. I suggest that RhoD can supress cell contraction in uninfected and ∆F11L-infected cells by inhibiting RhoC activation, and suggest that RhoD signalling is inhibited during infection to allow for efficient cell contraction.
Supervisor: Way, M. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available