6. B/Yamagata-lineage viruses showing RI or HRI
Eight (0.3%) B/Yamagata-lineage viruses out of 2311 tested
showed RI or HRI by one or more of the NAIs (Fig. 2 and Table 1).
One B/Yamagata-lineage virus from Macau, China contained an
NA H273Y substitution which conferred HRI (103-fold increase)
by peramivir and RI (7.1-fold increase) by oseltamivir but had no
effect on susceptibility to zanamivir and laninamivir (Table 1).
The two viruses carrying NA D197N substitution yielded different
patterns of NI and RI by all NAIs, around the intersect between NI
and RI categories; only for peramivir did both show RI. The NA
D197N substitution has been observed before in B/Yamagata-lineage
virus and shown to confer RI by zanamivir and peramivir
(Oakley et al., 2010). One of the two D197N variant viruses, came
from a patient during treatment with zanamivir, but no information
was available for the second patient. NA amino acid substitutions
N151T and S249N were detected in viruses with elevated IC50 values
(Table 1). The clinical specimen yielding the S249N variant also
contained the substitution. The clinical specimen yielding the
N151T variant did not contain the substitution. Further investigation
is needed to assess the role of these substitutions in altering
NAI susceptibility. Three B/Yamagata-lineage viruses had IC50 values
that were around the intersect between NI and RI categories,
but NA-gene sequencing revealed no NA amino acid substitutions.