"INFLUENZA PANDEMIC (H1N1) 2009 (58): THE NETHERLANDS, PB2 MUTATION
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A ProMED-mail post
Date: Mon 28 Sep 2009
From: Marion Koopmans
We would like to report 2 patients in The Netherlands, diagnosed with
influenza pandemic A(H1N1) 2009 virus infection that had a mutation (E627K)
in the basic polymerase 2 (PB2) protein. This mutation has previously been
associated with increased efficiency of replication and possible virulence
changes in other influenza A viruses.
The investigation identified a specific geographic region in the north of
The Netherlands as the place where viruses with the same genetic background
have circulated between mid July and mid August [2009]. No other cases
carrying the PB2 mutation have been identified.
On 15 Sep 2009, the 1st influenza A(H1N1)v virus with a glutamic acid to
lysine mutation at position 627 (E627K) in PB2 was identified through
routine sequence analysis of clinical samples from a diabetic patient
infected with A(H1N1)v virus. The 1st day of illness was on 9 Aug 2009,
when the patient was vacationing on one of the West Frisian Islands in the
wetlands north of The Netherlands (Waddenzee). He had a relatively mild
course of illness. Subsequent retrospective tracing of geographically
linked A(H1N1)v cases from the national databases led to the identification
of 24 additional A(H1N1)v confirmed cases throughout the country that had
stayed on the same popular holiday island during July and August. Sequence
analysis of 12/24 clinical specimen available at the institute identified
10 A(H1N1)v viruses that clustered with the virus obtained from the
diabetic index patient based on unique mutations in the NA gene and PB2
gene. Only one of these had the PB2 E627K mutation. This virus was isolated
from a family contact of an adolescent girl who returned from a one-week
stay on the same island on Mon 20 Jul 2009 with high fever and coughing.
This girl had been camping with a group of 16 boys and 8 girls that shared
2 tents. Almost all members of this group reportedly had been ill, and
influenza A(H1N1)v infection had been diagnosed in 2 other persons
belonging to the same camp. The girl was ill for a week, with full recovery
after 2 weeks. Our 2nd case with a virus shedding carrying the PB2 mutation
is the younger sister and became ill on Thu 23 Jul 2009. She was treated
with oseltamivir and recovered fully after one week. Both parents remained
free from symptoms.
As the mutations were identified more than one month after initial
detection, no further contact investigations were done. Municipal health
services were informed about the local disease activity. Since 15 Aug 2009,
mild influenza cases are no longer notifiable in The Netherlands, so we
have no information on possible onward transmission. No clusters of illness
(for example, from schools) were reported in the health regions involved
(including the island), and surveillance data from a national
physician-based sentinel network showed low ILI activity for the
Netherlands. Samples from 22 patients hospitalized with influenza A(H1N1)
in July and August did not have the PB2 mutation.
PB2 627K is consistently found in human influenza A viruses, but rarely in
avian-derived viruses. The E627K mutation may result in enhanced virus
replication efficiency in humans, possibly by adjustment to host body
temperature or cellular cofactors, and has previously been shown to be
associated with fatal cases of HPAI H5N1 and H7N7 virus infection in
humans. Until now, A(H1N1)v viruses with Influenza pandemic (H1N1) 2009
(57): in PB2 have not been reported, and the clinical and epidemiological
relevance of our finding remains unclear.
Preliminary experiments in ferrets using reverse genetics-derived new
influenza A(H1N1)v viruses with the E267K mutation in PB2 did not indicate
increased shedding, virulence or transmissibility. Further experiments as
well as increased molecular surveillance to monitor the situation are ongoing.
communicated by:
Marion Koopmans
Chief of Virology
Laboratory for Infectious Diseases and Screening, Center for Infectious
Disease Control
National Institute of Public Health
The Netherlands
[ProMED-mail thanks Dr Koopmans and colleagues for providing this
interesting information recording the detection of the same E267K mutation
in the basic polymerase 2 (PB2) protein of 2 independent isolates of
A(H1N1)v in the north of The Netherlands. The functional relevance of this
mutation remains to be determined. - Mod.CP]"
