1. Identification of Indonesian clade 2.1 highly pathogenic influenza A(H5N1) viruses with N294S and S246N neuraminidase substitutions which further reduce oseltamivir susceptibility
- Author
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Jennifer L. McKimm-Breschkin, Nining Hartaningsih, Susan Barrett, Muhammad Azhar, Frank Y. K. Wong, Paul Selleck, Kelly R. Davies, James McGrane, and Pudjiatmoko
- Subjects
0301 basic medicine ,Oseltamivir ,Genotype ,medicine.drug_class ,viruses ,Mutation, Missense ,Neuraminidase ,Microbial Sensitivity Tests ,medicine.disease_cause ,Antiviral Agents ,Virus ,Inhibitory Concentration 50 ,Viral Proteins ,03 medical and health sciences ,chemistry.chemical_compound ,Zanamivir ,Virology ,Drug Resistance, Viral ,Influenza A virus ,medicine ,Animals ,Pharmacology ,Influenza A Virus, H5N1 Subtype ,biology ,Neuraminidase inhibitor ,virus diseases ,Influenza A virus subtype H5N1 ,respiratory tract diseases ,030104 developmental biology ,chemistry ,Indonesia ,Influenza in Birds ,biology.protein ,Peramivir ,Chickens ,medicine.drug - Abstract
We have tested the in vitro susceptibility to the neuraminidase (NA) inhibitors of 96 highly pathogenic clade 2.1 A(H5N1) viruses from Indonesia, isolated between 2008 and 2011. HPAI virus samples obtained through the Influenza Virus Monitoring (IVM) surveillance program in Indonesia were tested for susceptibility to oseltamivir and zanamivir. The NAs of four viruses were identified as extreme outliers to oseltamivir, based on statistical analysis by box plots, with IC50 values ranging from 46 to 62 nM. The NAs of two of these viruses from Sumatra and Aceh, had an N294S substitution, while one virus from Sulawesi had an S246N NA substitution. The NAs of all four viruses showed a specific loss of slow binding to oseltamivir in an IC50 kinetics assay. As observed in our previous surveillance, there was only a minimal effect on the sensitivity to zanamivir or peramivir for these mutants or any of the other isolates tested. The continued circulation of subtype H5N1 viruses in avian species poses an on-going zoonotic threat. The fact that we continue to identify avian isolates with naturally occurring mutations conferring reduced oseltamivir susceptibility remains a concern, given oseltamivir will be a key antiviral in the event of a new pandemic emerging.
- Published
- 2018