Details

Autor(en) / Beteiligte

• McKimm-Breschkin, Jennifer L.
• Barrett, Susan
• Wong, Frank Y.K.
• Pudjiatmoko
• Azhar, Muhammad
• Selleck, Paul
• Davies, Kelly R.
• Hartaningsih, Nining
• McGrane, James

Titel

Identification of Indonesian clade 2.1 highly pathogenic influenza A(H5N1) viruses with N294S and S246N neuraminidase substitutions which further reduce oseltamivir susceptibility

Ist Teil von

• Antiviral research, 2018-05, Vol.153, p.95-100

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •Susceptibilities to the NAIs of 96 HPAI clade 2.1 (H5N1) viruses from Indonesia were tested in an enzyme assay.•Box Plot analysis identified 4 viruses as extreme outliers to oseltamivir with IC50 values ranging from 46 to 62 nM.•Two of the NAs had an N294S substitution, one had an S246N substitution.•There was minimal effect on sensitivity to zanamivir or peramivir for any of the isolates, including the mutants.