Rare influenza A (H3N2) variants with reduced sensitivity to antiviral drugs

Abstract

In 2007 and 2008 in Myanmar, we detected influenza viruses A (H3N2) that exhibited reduced sensitivity to both zanamivir and amantadine. These rare and naturally occurring viruses harbored a novel Q136K mutation in neuraminidase and S31N mutation in M2.

Figure 1

Phylogenetic analysis of the hemagglutinin (HA) (A) and neuraminidase (B) genes of influenza virus A (H3N2) isolates in Myanmar in 2007 and 2008. Trees were generated by using the neighbor-joining method. Bootstrap values >70% of 1,000 replicates and amino acid changes that characterize a branch are indicated on the left side of the node. Amantadine-resistant isolates with S31N mutation in M2 are marked with asterisks, and isolates with reduced sensitivity to zanamivir with Q136K mutation in NA are marked with squares. GenBank accession no. of the genomic sequences of isolates are GQ478849–GQ478866. Nucleotide sequences of the HA and NA genes of vaccine strains and isolates from other countries were obtained from the National Center for Biotechnology Information Influenza Virus Resource (www.ncbi.nlm.nih.gov/genomes/FLU). Scale bar indicates nucleotide substitutions per site.

Figure 2

Detection of Q136K substitution in NA by sequencing in primary samples and virus isolates. Arrows indicate the first peak of the codon encoding amino acid position 136. Comparison of the sequence chromatogram showed a mixed population of bases in both original clinical samples and virus isolates, with a dominant peak for 136K (AAG) mutants, compared with wild-type 136Q (CAG) viruses. NA, neuraminidase.