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Identification of novel immunomodulators in the human poxvirus molluscum contagiosum virus (MCV IMMUNOREGULATION)
Date du début: 1 mars 2013, Date de fin: 28 févr. 2015 PROJET  TERMINÉ 

"Infectious diseases kill 16 million people world-wide each year. Understanding how the immune system functions to sense and fight pathogens is essential for the development of novel therapeutics. Poxviruses have evolved a wide-spectrum of open-reading frames (ORFs) encoding immunoregulators which bind host proteins and disrupt the antiviral immune response. These ORFs are acquired from the host and are incorporated into the terminal regions of the viral genome. The acquisition of this extensive ‘toolbox’ of immunoregulatory sequences over long periods of host-virus co-evolution make them highly incisive tools for revealing novel facets of host immune system under the continual selective pressure of pathogens. Most research on poxviral immunoregulation has been conducted using the genome of Vaccinia virus (VV), a virus that is not adapted to human infection. Molluscum Contagiosum virus (MCV), is the only known human–adapted poxvirus and causes a long-term infection with a relatively weak immune response from the host. It has a highly diverse genome with largely unique terminal ORFs only 10% of which currently have a known function. In this proposal, the Fellow will adopt biochemical and cell biology approaches to analyse the unique ORFs of MCV and identify sequences that modulate human anti-viral immunity. These viral immunoregulators will be characterised and used as a basis for the development of immunotherapeutics. This proposal is designed to utilize the strengths of both the Fellow and the Host lab to facilitate mutual transfer of knowledge and expertise for both parties. The host lab has a strong interest in studying poxviral immunoregulation, and the Fellow will provide the expertise and tools to allow these studies to yield novel findings. In turn, the Fellow will obtain knowledge and technical expertise in a world-class innate immunity lab, which will help him expand his research network, attain an independent position and advance his career. "