| Avian influenza virus H5N1 might be a threat to humans and arouse the next pandemic because of its virulence to cuase pultry to death and its ability to infection with human. Mutations conferring resistance to the adamantanes, amantadine and rimantadine, were detected in the majority of H5N1 viruses in Vietnam, Thailand and Cambodia during 2004-2005 but were less prevalent among H5N1 viruses of other genetic lineages (China and Indonesia). 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 have known neuraminidase inhibitor resistance mutations.Our previous study identified a dual mutation motif, L26I plus S31N, on the M2 gene of all amantadine-resistant H5N1 viruses isolated in Vietnam, Thailand and Cambodia during 2004-2005. However no isolates carrying the same dual L26I plus S31N mutation were detected in other H5N1 affected countries. We found that influenza viruses carrying the dual mutations seem to replicate better at higher temperatures (37oC and 40oC) than otherwise genetically identical viruses without these mutations. This may contribute to the expansion of viruses carrying these mutations in avian which typically have core-body temperatures higher than 37oC. The most common amantadine resistance mutation, S31N, is observed to be more prevalent in H5N1 than in other avian virus subtypes, H9N2 and H6N1, isolated from Southern China during the same time-period. We suggest that S31N in avian H5N1 influenza virus is a naturally occurring mutation which may be associated with virus host adaptation.It is still not clear whether the NA1 gene neuraminidase mutation, H274Y, detected in H5N1 infected human cases originated during disease treatment or came from the avian virus source. A/chicken/HongKong/3123.1/2002 (H5N1) isolate was found to contain the H274Y mutation on NA1 and resistance to oseltamivir was confirmed using a cell-based assay. To investigate if H274Y might naturally occur at low levels mixed with wild type in H5N1 poultry infections we examined 311 isolates from different hosts and geographical locations using a differential RT-PCR assay. The H274Y quasi species was more frequently recognized in isolates from infected chickens than in isolates from ducks and geese, but no geographical difference was observed. Passage H274Y mutant virus in mammalian and avian cell backgrounds also indicated that the H274Y mutant might be subject to host selection. |
