Identification of a human influenza type B strain with reduced sensitivity to neuraminidase inhibitor drugs.
A total of 126 influenza B isolates isolated between 1998 and 2002 from Australasia and the Asia-Pacific region were tested for their sensitivity to the neuraminidase (NA) inhibitor drugs zanamivir and oseltamivir carboxylate using a fluorescence-based enzyme assay. The mean (+/-1 S.D.) 50% inhibitory concentration (IC50) of the influenza B viruses tested was 1.41+/-0.53 nM against zanamivir and 14.91+/-14.31 nM with oseltamivir carboxylate. However, a single type B isolate (B/Perth/211/2001) from an infant who had not been treated with either of the NA inhibitor drugs, showed a nine-fold lower sensitivity to zanamivir and a 14-fold lower sensitivity to oseltamivir carboxylate compared with the mean IC50 of influenza B strains. A decrease in sensitivity to oseltamivir carboxylate and RWJ-270201 was also seen in both: a chemiluminescent assay and a second different fluorescent assay. Sequence analysis of the haemagglutinin HA1 region and the neuraminidase gene of B/Perth/211/2001 revealed no amino acid changes in sites that have previously been reported to confer resistance to either of the NAI drugs. Further investigations are in progress to identify the basis for this reduced sensitivity.
Hurt
Aeron C
AC
WHO Collaborating Centre for Reference and Research on Influenza, 45 Poplar Road, Melbourne, Vic. 3052, Australia. aeron_hurt@csl.com.au
McKimm-Breschkin
Jennifer L
JL
McDonald
Mandy
M
Barr
Ian G
IG
Komadina
Naomi
N
Hampson
Alan W
AW
D000081:Acetamides / Q000494:pharmacology; D000146:Acids, Carbocyclic; D000998:Antiviral Agents / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006146:Guanidines; D006801:Humans; D007223:Infant; D009981:Influenza B virus / Q000145:classification* / Q000187:drug effects* / Q000302:isolation & purification; D008163:Luminescent Measurements; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir; D011714:Pyrans; D012794:Sialic Acids / Q000494:pharmacology; D053243:Zanamivir
D000081:Acetamides; D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D004791:Enzyme Inhibitors; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; D053139:Oseltamivir; D009439:Neuraminidase; D053243:Zanamivir; C414210:peramivir