Modulation of host immunity by human cytomegalovirus. (360G-Wellcome-090323_Z_09_Z)
HCMV has the largest genome of any characterised human virus (236kb). All 167 putative ORFs, 14 miRNAs and additional non-coding RNAs will be available in a newly-constructed adenovirus (Ad) vector library. In addition, HCMV deletion mutants encompassing > 80 ORFs have been generated. All HCMV genes will be screened in NK cell functional assays using a combination of the Ad vector library and HCMV mutants. Preliminary studies reveal that HCMV regulates expression of a subset of host cell functio ns implicated in NK cell recognition; the Ad library and HCMV mutants will be screened to identity the genes responsible. Novel reagents will be developed to expand the range of NK cell receptor:ligand interactions that can be screened. Furthermore, HCMV BAC (Bacterial Artificial Chromosome) technology will be developed to provide for conditional expression of essential immunomodulatory functions and enable experimentation in a broader range of cell types. The mechanism-of-action of novel NK cel l modulators will be determined, and ongoing studies exploring unexpected novel properties of UL18, UL40, UL135, UL141, US2 and US11 will be developed. The capacity of NK cells derived from asymptomatic carriers and patients with overt disease to control HCMV infection will be evaluated.
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Grant Details
| Amount Awarded | 1062032 |
| Applicant Surname | Wilkinson |
| Approval Committee | Immunology and Infectious Disease Funding Committee |
| Award Date | 2010-02-08T00:00:00+00:00 |
| Financial Year | 2009/10 |
| Grant Programme: Title | Programme Grant |
| Internal ID | 090323/Z/09/Z |
| Lead Applicant | Prof Gavin Wilkinson |
| Other Applicant(s) | Dr Peter Tomasec, Prof Eddie Wang |
| Partnership Value | 1062032 |
| Planned Dates: End Date | 2018-10-31T00:00:00+00:00 |
| Planned Dates: Start Date | 2010-10-01T00:00:00+00:00 |
| Recipient Org: Country | United Kingdom |
| Region | Wales |