%0 Journal Article %A Rudneva, Irina A. %A Ilyushina, Natalia A. %A Timofeeva, Tatiana A. %A Webster, Robert G. %A Kaverin, Nikolai V. %T Restoration of virulence of escape mutants of H5 and H9 influenza viruses by their readaptation to mice %D 2005 %J Journal of General Virology, %V 86 %N 10 %P 2831-2838 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.81185-0 %I Microbiology Society, %X Antigenic mapping of the haemagglutinin (HA) molecule of H5 and H9 influenza viruses by selecting escape mutants with monoclonal anti-HA antibodies and subjecting the selected viruses to immunological analysis and sequencing has previously been performed. The viruses used as wild-type strains were mouse-adapted variants of the original H5 and H9 isolates. Phenotypic characterization of the escape mutants revealed that the amino acid change in HA that conferred resistance to a monoclonal antibody was sometimes associated with additional effects, including decreased virulence for mice. In the present study, the low-virulence H5 and H9 escape mutants were readapted to mice. Analysis of the readapted variants revealed that the reacquisition of virulence was not necessarily achieved by reacquisition of the wild-type HA gene sequence, but was also associated either with the removal of a glycosylation site (the one acquired previously by the escape mutant) without the exact restoration of the initial wild-type amino acid sequence, or, for an H5 escape mutant that had no newly acquired glycosylation sites, with an additional amino acid change in a remote part of the HA molecule. The data suggest that such ‘compensating’ mutations, removing the damaging effects of antibody-selected amino acid changes, may be important in the course of influenza virus evolution. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81185-0