The winner of the 2006 AHMF Travel Scholarship is Gillian Scott. Gillian was awarded the scholarship to attend the 11th international CMV and Betaherpesvirus Workshop at the Universite Paul Sabatiere in Toulouse, France from May 13-17, 2007 and present “The CMV DNA Polymerase Aspartate Triad as an Antiviral Target”.
As well as going to the CMV conference Gillian was also able to visit collaborators of the project in Erlangen, Germany and Cambridge, UK, and give a talk to both of these groups on her research (including the poster presentation).
Research summary
Author(s):
Gillian M. Scott1,3,4 , Min Jun1,3 , Jenna M. Iwasenko1,4 , Heng Giap Woon1,3 , Hooi-Ling Ng5 , Craig Morton5 , Michael Parker5 and William D Rawlinson1,2,3,4
Virology Research, POWH and UNSW Research Laboratories
Department of Microbiology, SEALS, Prince of Wales Hospital, Randwick, NSW, Australia
School of Medical Sciences, Faculty of Medicine
School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, Australia
Biota Laboratories, St. Vincents Research Institute, Melbourne, Australia
Full title:
Identification of potential antiviral targets in the CMV DNA polymerase and other proteins involved in viral DNA replication
Publication details:
Presented at the 11th International CMV and Betaherpesvirus Workshop at the Universite Paul Sabatiere in Toulouse, France from May 13-17, 2007
Abstract:
Human cytomegalovirus (CMV) is a major pathogen of immunocompromised individuals including patients undergoing organ transplantation, and treatment of CMV infections can be complicated by the emergence of antiviral resistant strains. Our previous analyses of human and murine CMV demonstrated DNA polymerase mutations associated with antiviral resistance tended to cluster around an aspartate triad thought to be involved in catalysis (Scott, et. al. J Med Virol 2004; Scott, et. al. J Gen Virol. 2005). Analysis of CMV and murine CMV DNA polymerase models suggest these mutations cause small perturbations in the conformation of the human catalytic subunit. In vitro DNA polymerase activity assays are being developed to ascertain the exact impact these mutations have on the overall function of the CMV DNA polymerase. In silico screening of the CMV DNA polymerase models has identified 50 lead compounds that interact with, and potentially interfere with the DNA polymerase aspartate triad. These compounds are being analysed for their ability to inhibit the CMV DNA polymerase through in vitro activity assays, as well as the ability to inhibit CMV replication in plaque reduction assays and DNA yield reduction assays developed by our laboratory. Similar investigations of other CMV proteins involved in DNA replication such as the helicase-primase are also ongoing. Studies such as these are helping to elucidate the specific regions of these proteins that are important for DNA and CMV replication and provide novel targets for anti-CMV agents.
