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