Naturally occurring antiviral drug resistance in Avian H5N1 virus

Abstract

Resistance to the neuraminidase inhibitor, oseltamivir, was found in H5N1 virus isolated from infected patients in Vietnam but no recent avian H5N1 isolates have been reported to possess known neuraminidase inhibitor resistance mutations. It is still not clear whether the NA1 gene neuraminidase mutation, His274Tyr, detected in H5N1 infected human cases originated during disease treatment or came from the avian virus source. A 2002 HK chicken H5N1 isolate was found to contain the His274Tyr mutation on NA1 and resistance to oseltamivir was confirmed using a cell-based assay. To investigate if His274Tyr might naturally occur at low levels mixed with wild type in H5N1 poultry infections we examined isolates from different hosts and geographical locations using a differential RT-PCR assay. The His274Ty quasi species was more frequently recognized in isolates from infected chickens than in isolates from ducks and geese, but no geographical difference was observed. Close surveillance of mutants in the virus population, combined with pursuit of alternative therapies, is essential to H5N1 pandemic containment strategies.