File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Neuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility

TitleNeuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibility
Authors
Issue Date2005
Citation
Antimicrobial Agents And Chemotherapy, 2005, v. 49 n. 10, p. 4075-4084 How to Cite?
AbstractMutations of the conserved residues of influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease the sialidase activity and/or stability of the NA, thus compromising viral fitness. In fact, clinically derived NAI-resistant variants with different NA mutations have shown different transmissibilities in ferrets (M. L. Herlocher, R. Truscon, S. Elias, H. Yen, N. A. Roberts, S. E. Ohmit, and A. S. Monto, J. Infect. Dis. 190:1627-1630, 2004). Molecular characterization of mutant viruses that have a homogeneous genetic background is required to determine the effect of single mutations at conserved NA residues. We generated recombinant viruses containing either the wild-type NA (RG WT virus) or a single amino acid change at NA residue 119 (RG E119V-NA virus) or 292 (RG R292K-NA virus) in the A/Wuhan/359/95 (H3N2) influenza virus background by reverse genetics. Both mutants showed decreased sensitivity to oseltamivir carboxylate, and the RG R292K-NA virus showed cross-resistance to zanamivir. We also observed differences between the two mutants in NA enzymatic activity and thermostability. The R292K mutation caused greater reduction of sialidase activity and thermostability than the E119V mutation. The NA defect caused by the R292K mutation was associated with compromised growth and transmissibility, whereas the growth and transmissibility of the RG E119V-NA virus were comparable to those of RG WT virus. Our results suggest that NAI-resistant influenza virus variants may differ substantially in fitness and transmissibility, depending on different levels of NA functional loss. Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179786
ISSN
2015 Impact Factor: 4.415
2015 SCImago Journal Rankings: 2.322
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYen, HLen_US
dc.contributor.authorHerlocher, LMen_US
dc.contributor.authorHoffmann, Een_US
dc.contributor.authorMatrosovich, MNen_US
dc.contributor.authorMonto, ASen_US
dc.contributor.authorWebster, RGen_US
dc.contributor.authorGovorkova, EAen_US
dc.date.accessioned2012-12-19T10:04:42Z-
dc.date.available2012-12-19T10:04:42Z-
dc.date.issued2005en_US
dc.identifier.citationAntimicrobial Agents And Chemotherapy, 2005, v. 49 n. 10, p. 4075-4084en_US
dc.identifier.issn0066-4804en_US
dc.identifier.urihttp://hdl.handle.net/10722/179786-
dc.description.abstractMutations of the conserved residues of influenza virus neuraminidase (NA) that are associated with NA inhibitor (NAI) resistance decrease the sialidase activity and/or stability of the NA, thus compromising viral fitness. In fact, clinically derived NAI-resistant variants with different NA mutations have shown different transmissibilities in ferrets (M. L. Herlocher, R. Truscon, S. Elias, H. Yen, N. A. Roberts, S. E. Ohmit, and A. S. Monto, J. Infect. Dis. 190:1627-1630, 2004). Molecular characterization of mutant viruses that have a homogeneous genetic background is required to determine the effect of single mutations at conserved NA residues. We generated recombinant viruses containing either the wild-type NA (RG WT virus) or a single amino acid change at NA residue 119 (RG E119V-NA virus) or 292 (RG R292K-NA virus) in the A/Wuhan/359/95 (H3N2) influenza virus background by reverse genetics. Both mutants showed decreased sensitivity to oseltamivir carboxylate, and the RG R292K-NA virus showed cross-resistance to zanamivir. We also observed differences between the two mutants in NA enzymatic activity and thermostability. The R292K mutation caused greater reduction of sialidase activity and thermostability than the E119V mutation. The NA defect caused by the R292K mutation was associated with compromised growth and transmissibility, whereas the growth and transmissibility of the RG E119V-NA virus were comparable to those of RG WT virus. Our results suggest that NAI-resistant influenza virus variants may differ substantially in fitness and transmissibility, depending on different levels of NA functional loss. Copyright © 2005, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.relation.ispartofAntimicrobial Agents and Chemotherapyen_US
dc.subject.meshAcetamides - Pharmacologyen_US
dc.subject.meshAmino Acid Substitutionen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCoculture Techniquesen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDrug Resistance, Multipleen_US
dc.subject.meshDrug Resistance, Viral - Drug Effects - Genetics - Physiologyen_US
dc.subject.meshDrug Toleranceen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshEnzyme Stability - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFerretsen_US
dc.subject.meshGenetic Variationen_US
dc.subject.meshGuanidines - Pharmacologyen_US
dc.subject.meshKineticsen_US
dc.subject.meshMutagenesis, Site-Directeden_US
dc.subject.meshNeuraminidase - Antagonists & Inhibitors - Genetics - Metabolismen_US
dc.subject.meshOrthomyxoviridae - Drug Effects - Enzymology - Genetics - Growth & Developmenten_US
dc.subject.meshOrthomyxoviridae Infections - Transmissionen_US
dc.subject.meshOseltamiviren_US
dc.subject.meshPyrans - Pharmacologyen_US
dc.subject.meshRecombination, Geneticen_US
dc.subject.meshSialic Acids - Pharmacologyen_US
dc.subject.meshTemperatureen_US
dc.subject.meshVirus Replication - Geneticsen_US
dc.subject.meshZanamiviren_US
dc.titleNeuraminidase inhibitor-resistant influenza viruses may differ substantially in fitness and transmissibilityen_US
dc.typeArticleen_US
dc.identifier.emailYen, HL: hyen@hku.hken_US
dc.identifier.authorityYen, HL=rp00304en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/AAC.49.10.4075-4084.2005en_US
dc.identifier.pmid16189083-
dc.identifier.scopuseid_2-s2.0-25844474747en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-25844474747&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume49en_US
dc.identifier.issue10en_US
dc.identifier.spage4075en_US
dc.identifier.epage4084en_US
dc.identifier.isiWOS:000232244700013-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYen, HL=7102476668en_US
dc.identifier.scopusauthoridHerlocher, LM=8866157900en_US
dc.identifier.scopusauthoridHoffmann, E=7201369718en_US
dc.identifier.scopusauthoridMatrosovich, MN=7005500591en_US
dc.identifier.scopusauthoridMonto, AS=7004552306en_US
dc.identifier.scopusauthoridWebster, RG=36048363100en_US
dc.identifier.scopusauthoridGovorkova, EA=7003837718en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats