Role of human herpesvirus 8 K5 gene product in the pathogenesis of pulmonary arterial hypertension. (360G-Wellcome-078885_Z_05_Z)

£183,726

Identification of heterozygous germline mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR-II) in familial pulmonary arterial hypertension (PAH) is a major advance in understanding this condition. Our laboratory, and others, has demonstrated that a reduction in BMP receptor signalling is a feature common to many forms of PAH, even in the absence of identifiable mutations in the BMPR2 gene. Thus, factors that reduceBMP receptor expression or function may be critical to PAH pathogenesis. Recently human herpersvirus-8 (HHV-8) was identified in the pulmonary vasculature of 60% of cases of idiopathic PAH. Like other herpesviruses HHV-8 expresses immunoevasion genes. We (PJL) have shown that the HHV-8 encoded K3 and K5 genes ubiquitinate endogenous immunoreceptors, targeting them for endolysosomal degradation. Our preliminary data shows that K5 interferes with cell surface expression of BMP receptors. This is the first demonstration of aherpesvirus gene product subverting growth factor receptor expression. The original hypothesis underpinning these studies is that ubiquitination and

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Grant Details

Amount Awarded 183726
Applicant Surname Durrington
Approval Committee Clinical Interview Committee
Award Date 2006-04-03T00:00:00+00:00
Financial Year 2005/06
Grant Programme: Title Research Training Fellowship
Internal ID 078885/Z/05/Z
Lead Applicant Dr Hannah Durrington
Partnership Value 183726
Planned Dates: End Date 2009-07-09T00:00:00+00:00
Planned Dates: Start Date 2006-07-10T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Edwin Chilvers