A novel role of the KSHV ORF57 protein in translation enhancement. (360G-Wellcome-086168_Z_08_Z)

£120,719

KSHV is the most recently identified human tumour virus. It is the etiological agent of all forms of Kaposi s sarcoma. KSHV has two distinct forms of infection, latency and lytic replication. Although latency has been implicated in tumourigenesis, lytic replication plays an important part in the pathogenesis and spread of KSHV infection. Therefore, for a better understanding of KSHV pathogenesis it is essential to study the molecular mechanisms which regulate lytic gene expression and replicatio n. The KSHV ORF57 protein plays a pivotal role in KSHV mRNA processing. It binds intronless KSHV mRNAs and recruits the cellular hTREX complex which in turn allows efficient nuclear export of intronless viral transcripts. We now wish to investigate a second function of KSHV ORF57, namely its role in the translation enhancement of intronless viral transcripts. Specifically we aim to determine whether KSHV ORF57 functions in translation enhancement by recruiting essential cellular translation factors, such as the 48S preinitiation complex, via an interaction with the cellular protein PYM. Moreover, we will determine how KSHV ORF57 regulates the ability to interact with two separate multiple protein cellular complexes, namely hTREX and the PYM/48S preinitiation complex, to perform its multiple functions.

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Grant Details

Amount Awarded 120719
Applicant Surname Whitehouse
Approval Committee Immunology and Infectious Disease Funding Committee
Award Date 2008-10-02T00:00:00+00:00
Financial Year 2008/09
Grant Programme: Title Project Grant
Internal ID 086168/Z/08/Z
Lead Applicant Prof Adrian Whitehouse
Partnership Value 120719
Planned Dates: End Date 2011-04-05T00:00:00+00:00
Planned Dates: Start Date 2009-04-06T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Yorkshire and the Humber