Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1002276
Title: Multidrug resistant 2009 a/h1n1 influenza clinical isolate with a neuraminidase i223r mutation retains its virulence and transmissibility in ferrets
Authors: van der Vries E.
Kroeze E.J.
Stittelaar K.J.
Linster M. 
van der Linden A.
Schrauwen E.J.A.
Leijten L.M.
van Amerongen G.
Schutten M.
Kuiken T.
Osterhaus A.D.M.E.
Fouchier R.A.M.
Boucher C.A.B.
Herfst S.
Keywords: arginine
isoleucine
oseltamivir
peramivir
zanamivir
sialidase
2009 H1N1 influenza
aerosol
animal cell
animal experiment
animal model
animal tissue
article
cell strain
cross resistance
ferret
in vitro study
Influenza virus A H1N1
inoculation
lung alveolitis
lung lesion
multidrug resistance
mutation
nonhuman
pathogenesis
virus isolation
virus mutant
virus replication
virus strain
virus transmission
virus virulence
weight reduction
animal
cell line
disease model
disease transmission
dog
enzymology
genetics
human
influenza
Influenza virus A H1N1
metabolism
mutation
orthomyxovirus infection
pandemic
pathogenicity
Animalia
Mustela
Orthomyxoviridae
Animals
Cell Line
Disease Models, Animal
Dogs
Drug Resistance, Multiple, Viral
Ferrets
Humans
Influenza A Virus, H1N1 Subtype
Influenza, Human
Mutation
Neuraminidase
Orthomyxoviridae Infections
Pandemics
Issue Date: 2011
Citation: van der Vries E., Kroeze E.J., Stittelaar K.J., Linster M., van der Linden A., Schrauwen E.J.A., Leijten L.M., van Amerongen G., Schutten M., Kuiken T., Osterhaus A.D.M.E., Fouchier R.A.M., Boucher C.A.B., Herfst S. (2011). Multidrug resistant 2009 a/h1n1 influenza clinical isolate with a neuraminidase i223r mutation retains its virulence and transmissibility in ferrets. PLoS Pathogens 7 (9) : e1002276. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1002276
Rights: Attribution 4.0 International
Abstract: Only two classes of antiviral drugs, neuraminidase inhibitors and adamantanes, are approved for prophylaxis and therapy against influenza virus infections. A major concern is that influenza virus becomes resistant to these antiviral drugs and spreads in the human population. The 2009 pandemic A/H1N1 influenza virus is naturally resistant to adamantanes. Recently a novel neuraminidase I223R mutation was identified in an A/H1N1 virus showing cross-resistance to the neuraminidase inhibitors oseltamivir, zanamivir and peramivir. However, the ability of this virus to cause disease and spread in the human population is unknown. Therefore, this clinical isolate (NL/2631-R223) was compared with a well-characterized reference virus (NL/602). In vitro experiments showed that NL/2631-I223R replicated as well as NL/602 in MDCK cells. In a ferret pathogenesis model, body weight loss was similar in animals inoculated with NL/2631-R223 or NL/602. In addition, pulmonary lesions were similar at day 4 post inoculation. However, at day 7 post inoculation, NL/2631-R223 caused milder pulmonary lesions and degree of alveolitis than NL/602. This indicated that the mutant virus was less pathogenic. Both NL/2631-R223 and a recombinant virus with a single I223R change (recNL/602-I223R), transmitted among ferrets by aerosols, despite observed attenuation of recNL/602-I223R in vitro. In conclusion, the I223R mutated virus isolate has comparable replicative ability and transmissibility, but lower pathogenicity than the reference virus based on these in vivo studies. This implies that the 2009 pandemic influenza A/H1N1 virus subtype with an isoleucine to arginine change at position 223 in the neuraminidase has the potential to spread in the human population. It is important to be vigilant for this mutation in influenza surveillance and to continue efforts to increase the arsenal of antiviral drugs to combat influenza. © 2011 van der Vries et al.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/161653
ISSN: 15537366
DOI: 10.1371/journal.ppat.1002276
Rights: Attribution 4.0 International
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