Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5822033 | Antiviral Research | 2015 | 5 Pages |
â¢Influenza A/Brisbane/59/07 (H1N1) variants maintain their viral fitness despite the H275Y neuraminidase (NA) mutation.â¢The R222Q NA substitution has a permissive role for oseltamivir-resistant A/Brisbane/59/07-H275Y variants.â¢The permissive role of the R222Q substitution is also shown for the influenza A/Mississippi/03/2001 H275Y variant.â¢Changes in non-NA segments are unlikely to play a major permissive effect in seasonal A(H1N1)-H275Y viruses in vitro.
Permissive neuraminidase (NA) substitutions such as R222Q, V234M and D344N have facilitated the emergence and worldwide spread of oseltamivir-resistant influenza A/Brisbane/59/2007 (H1N1)-H275Y viruses. However, the potential contribution of genetic changes in other viral segments on viral fitness remains poorly investigated. A series of recombinant A(H1N1)pdm09 and A/WSN/33 7:1 reassortants containing the wild-type (WT) A/Brisbane/59/2007 NA gene or its single (H275Y) and double (H275Y/Q222R, H275Y/M234V and H275Y/N344D) variants were generated and their replicative properties were assessed in vitro. The Q222R reversion substitution significantly reduced viral titers when evaluated in both A(H1N1)pdm09 and A/WSN/33 backgrounds. The permissive role of the R222Q was further confirmed using A/WSN/33 7:1 reassortants containing the NA gene of the oseltamivir-susceptible or oseltamivir-resistant influenza A/Mississippi/03/2001 strains. Therefore, NA permissive substitutions play a dominant role for improving viral replication of oseltamivir-resistant A (H1N1)-H275Y viruses in vitro.