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The role of innate immune regulation in viral pathogenesis and the development of anti-viral T cell memory (360G-Wellcome-207503_Z_17_Z)

Immune mechanisms that regulate antiviral immune responses determine whether the host can control pathogen replication and virus-induced immunopathology. The pathogenic human cytomegalovirus (HCMV) establishes chronicity and induces inflammation-associated pathologies. Cytomegalovirus (CMV) also induces the largest known expansion of T cells, and thus represents an important tool for identifying mechanisms inducing robust T cell immunity. CMV may also be exploited as an attenuated vaccine vector. Using a CMV model of viral pathogenesis, I identified that immune regulation during initial infection determines the extent of virus-induced inflammation and development of long-lived virus-specific immunity. The key goals of this proposal are: Identify innate immune components that mediate viral pathogenesis and understand how they are controlled Test whether innate immune pathways can be a) safely targeted therapeutically to treat viral disease and/or b) used to predict genetic risk of CMV pathogenesis Identify the early immunological events that promote CMV-specific T cell memory development, and elucidate whether regulatory pathways controlling these factors can be harnessed to enhance virus-driven memory T cell formation induced by attenuated viral vectors This research will determine whether innate immune activation can be exploited to: 1) safely treat viral pathogenesis and/or 2) enhance virus-induced T cell memory responses.

£1,942,612

11 Jul 2017

Grant details
Amount Awarded 1942612
Applicant Surname Humphreys
Approval Committee Science Interview Panel
Award Date 2017-07-11T00:00:00+00:00
Financial Year 2016/17
Grant Programme: Title Senior Research Fellowship Basic Renewal
Internal ID 207503/Z/17/Z
Lead Applicant Dr Ian Humphreys
Planned Dates: End Date 2022-10-01T00:00:00+00:00
Planned Dates: Start Date 2017-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Wales
Sponsor(s) Prof Simon Jones
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