Grant: Operating Grant

Herpesviruses such as herpes simplex virus and cytomegalovirus frequently and persistently infect humans, which may lead to recurrent and/or severe diseases particularly in immunocompromised individuals (HIV-infected and transplant patients). A few antiviral agents have been developed against herpesviruses and are used either for treatment of established disease or prevention in high-risk patients. The frequent use of these antivirals in immunocompromised subjects has led to the development of drug-resistant viruses, some of which are fully pathogenic. In this research program, we will investigate the mechanisms of resistance of herpesviruses against acyclovir/ganciclovir (nucleoside analogues) and against foscarnet (a pyrophosphate analogue) at the molecular and enzymatic levels with a focus on DNA polymerase mutations using clinical isolates collected in previous antiviral trials and recombinant viruses generated in our laboratory. Our studies should improve the management of drug-resistant herpesvirus infections, a major cause of morbidity in the Canadian population, through a more rationale use of current antiviral agents and development of compounds with new mechanisms of action.