Farrukee R, Butler J, Reading PC, Hurt AC. Characterization of substitutions in the neuraminidase of A(H7N9) influenza viruses selected following serial passage in the presence of different neuraminidase inhibitors. Antiviral Res. 2019 May 24.
Avian A(H7N9) infections in humans have been reported in China since 2013 and are of public health concern due to their severity and pandemic potential. Oseltamivir and peramivir are neuraminidase inhibitors (NAIs) routinely used for the treatment of A(H7N9) infections, but variants with reduced sensitivity to these drugs can emerge in patients during treatment. Zanamivir and laninamivir are NAIs that are used less frequently. Herein, we performed in vitro serial passaging experiments with recombinant viruses, containing the neuraminidase (NA) from influenza A/Anhui/1/13 (H7N9) virus, in the presence of each NAI, to determine whether variants with reduced sensitivity would emerge. NA substitutions were characterized for their effect on the NA enzymatic activity and surface expression of the A/Anhui/1/13 (Anhui/1) NA, as well as NAs originating from contemporary A(H7N9) viruses of the Yangtze River Delta and Pearl River Delta lineages. In vitro passage in the presence of oseltamivir, peramivir and laninamivir selected for substitutions associated with reduced sensitivity (E119D, R292K and R152K), whereas passage in the presence of zanamivir did not select for any viruses with reduced sensitivity. All the NA substitutions significantly reduced activity, but not the expression of the Anhui/1 NA. In contemporary N9 NAs, all substitutions tested significantly reduced NA enzyme function in the Yangtze River lineage background, but not in the Pearl River Delta lineage background. Overall, these findings suggest that zanamivir may be less likely than the other NAIs to select for resistance in A(H7N9) viruses and that the impact of substitutions that reduce NAI susceptibility or enzyme function may be less in A(H7N9) viruses from the Pearl River lineage.
See Also:
Latest articles in those days:
- Structures of H5N1 influenza polymerase with ANP32B reveal mechanisms of genome replication and host adaptation 2 days ago
- Risk assessment of a highly pathogenic H5N1 influenza virus from mink 2 days ago
- Detection of clade 2.3.4.4b highly pathogenic H5N1 influenza virus in New York City 2 days ago
- Sequence-based epitope mapping of high pathogenicity avian influenza H5 clade 2.3.4.4b in Latin America 3 days ago
- Guanylate-binding protein 1 inhibits inflammatory factors produced by H5N1 virus through Its GTPase activity 3 days ago
[Go Top] [Close Window]