Abstract
The prevention and control of influenza with vaccines and antiviral drugs is of great importance. M2 inhibitors, amantadine and rimantadine have been extensively used in some countries. The next generation of antiviral drugs, neuraminidase (NA) inhibitors oseltamivir and zanamivir, are being stockpiled for a potential influenza pandemic. The emergence of resistant strains is thus an important issue. The purpose of this study was to examine the sensitivity to M2 and NA inhibitors of Greek influenza A(H3N2) strains isolated during three influenza seasons between 2004 and 2008 and to determine the phylogenetic clades of those strains. M2 and NA sequences of 34 patient isolates were checked for known resistance mutations. In addition, haemagglutinin (HA) sequences were used to determine the phylogenetic relationship between resistant and sensitive strains. All influenza A(H3N2) strains isolated during the season 2004-5 were found susceptible to adamantanes, bearing the S31N mutation, compared to 88% of the strains isolated in 2005-6 and 75% of the strains isolated in 2006-7. Molecular analysis of the HA gene showed a correlation of the mutants with specific phylogenetic clades. No known mutations in the NA or HA gene that have been implicated in resistance to NA inhibitors were found in the A(H3N2) strains isolated in the three influenza seasons. Despite the fact that amantadine is the only drug approved for prophylaxis in Greece, it has not been extensively used. So it seems that resistant strains circulating in the area after 2005 followed the global trend of replacement of susceptible strains by resistant ones. Oseltamivir and zanamivir are currently approved only for therapeutic use in Greece and has not been extensively used either.
Highlights
The prevention and control of influenza through the use of vaccines and antiviral drugs is of great importance
This study included molecular analysis of the M2, NA and HA genes of influenza A(H3N2) strains that were isolated in northern Greece during the last three influenza seasons
Nor did we find known mutations in the HA gene that have been implicated in resistance to NA inhibitors
Summary
The prevention and control of influenza through the use of vaccines and antiviral drugs is of great importance. Adamantanes, amantadine and rimantadine, are inhibitors of influenza A virus M2 protein They were the first antiviral drugs licensed for treatment and prophylaxis of influenza A infections and have been extensively used in some countries. Various mutations have been implicated in the resistance to oseltamivir and/or zanamivir, the most common being amino acid substitutions at positions 119, 222, 274, 292 and 294, and a deletion at positions 244-247 of the NA gene. It is under investigation whether specific mutations at positions 198, 229 and 262 in the haemagglutinin (HA) gene could correlate with the resistance of influenza viruses to NA inhibitors [4-6]. The purpose of this study was to examine the sensitivity to M2 and NA inhibitors of Greek influenza A(H3N2) strains isolated during the influenza seasons between 2004 and 2008, and to determine the phylogenetic relationship between those strains
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