Investigation into a novel mechanism regulating KSHV reactivation. (360G-Wellcome-079949_Z_06_Z)

£190,598

Kaposi s sarcoma associated herpesvirus virus (KSHV) is the most recently identified human tumour virus. It is the etiological agent of all forms of Kaposi s sarcoma and is also associated with AIDs-related lymproliferative diseases. KSHV has two distinct forms of infection, latent persistence and lytic replication. Although, latent persistence of the KSHV genome has been implicated in tumourigenesis, it is evident that lytic replication plays an important part in the pathogenesis of KSHV infect ion. Therefore, it is essential to study the molecular mechanisms of reactivation and the control of lytic gene expression for a better understanding of KSHV pathogenesis. The KSHV ORF 50 protein is the key transcriptional activating protein which regulates the latent-lytic switch. We have recently demonstrated that KSHV ORF 50 interacts with the cellular protein, Hey-1. This is a particular intriguing interaction, as Hey-1 is a transcriptional repressor protein. Herein, we aim to test the hy pothesis that ORF 50 interacts with Hey-1 to promote its degradation via the ubiquitin proteasome degradation pathway, specifically acting as an ubiquitin E3 ligase. Moreover, we aim to determine the role of Hey-1 in the KSHV latent-lytic switch and whether Hey-1 degradation is required for KSHV lytic replication.

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Grant Details

Amount Awarded 190598
Applicant Surname Whitehouse
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2006-07-06T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Project Grant
Internal ID 079949/Z/06/Z
Lead Applicant Prof Adrian Whitehouse
Other Applicant(s) Dr Eric Hewitt
Partnership Value 190598
Planned Dates: End Date 2009-12-31T00:00:00+00:00
Planned Dates: Start Date 2007-01-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber