Synthesis and purification of flavivirus-specific antiviral factor Mrasal [ 2003 - 2004 ]

Research Grant

Researchers: Dr Nadezda Urosevic (Principal investigator)

Brief description In this proposal we suggest to develop an anti-flaviviral compound based on naturally occurring host factors associated with inborn flavivirus resistance observed in mice. We propose to synthesise and purify a mouse protein factor encoded by a gene (Mrasal), which we have previously mapped by mouse genetics and positional cloning to a narrow 300 kb chromosomal region on mouse chromosome 5 carrying flavivirus resistance locus (Flv). When this mouse gene was isolated, sub cloned into a mammalian expression vector pcDNA3tag and transiently transfected and expressed in cos-7 and Vero cells, its product conferred antiviral effect to a flavivirus Murray Valley encephalitis (MVE), but not to a non-flavivirus encephalomyocarditis virus (EMCV). Mrasal protein operates as an antiviral host factor and confers a flavivirus specific resistance at the cellular level. It could be directly used for the treatment-cure of acute flavivirus infections in vivo. Our aims are to produce and purify the Mrasal protein for the in vivo delivery as a therapeutic compound into susceptible mice during the acute phase of flavivirus infection: 1.             To synthesise and purify Mrasal protein using baculovirus system. 2.             To encapsulate the protein into liposomes ready to be used in mice. 3.             To perform initial testing in a limited number of susceptible mice.

Funding Amount $AUD 140,000.00

Funding Scheme NHMRC Development Grants

Notes Development Grant