The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo

Ives, Jane; Carr, Jackie; Tai, Chun Y.; Lambkin, Robert; Kelly, Lauren; Oxford, John; Hayden, Frederick G.; Roberts, Noel A.

doi:10.1016/s0166-3542(02)00053-0

Cited by 345 publications

(276 citation statements)

References 21 publications

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“…Studies have shown that mutations that are part of the NA enzyme catalytic site or that surround it may impair virus fitness, and these mutations generally decrease susceptibility to neuraminidase inhibitors. In addition, human influenza virus isolates which harbor NA mutations that confer resistance to NA inhibitors have been generally attenuated in animal models (16,19). A recent study showed that a 2009 pandemic H1N1 isolate and its NA mutant counterpart, resistant to oseltamivir, caused a similar disease course in ferrets without apparent attenuation of clinical signs (8).…”

Section: Discussionmentioning

confidence: 99%

Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts

Smith

Nagy

Driskell

et al. 2011

J Virol

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Virus replication and pulmonary disease pathogenesis in ferrets following) were compared. Nasal wash virus titers were similar for Ncal99 and Sw30, with peak virus titers of 10 5.1 50% tissue culture infectious doses (TCID 50 )/ml and 10 5.5 TCID 50 /ml occurring at day 3 postinfection (p.i.), respectively. The mean peak titer for CA09 also occurred at day 3 p.i. but was higher (10 7 TCID 50 /ml). In contrast, the peak virus titers (10 3.6 to 10 4.3 TCID 50 /ml) for Mal08 were delayed, occurring between days 5 and 7 p.i. Disease pathogenesis was characterized by microscopic lesions in the nasal turbinates and lungs of all ferrets; however, Sw30 infection was associated with severe bronchointerstitial pneumonia. The results demonstrate that although CA09 is highly transmissible in the human population and replicates well in the ferret model, it causes modest disease compared to other H1N1 viruses, particularly Sw30 infection.

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Section: Discussionmentioning

confidence: 99%

Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts

Smith

Nagy

Driskell

et al. 2011

J Virol

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“…The mutant HA has lower affinity for its sialic acid ligands and the virus can escape from aggregation because of low affinity even though the NA is inactivated by the drug 70,71 . Resistance in natural isolates is associated with mutations in the NA, but mostly these resistant viruses are less fit, only appear sporadically, and do not spread 72 . However, seasonal H1N1 viruses with the H275Y (N1 numbering; H274Y in N2) mutation spread throughout the world in 2008, apparently because a compensating mutation had increased their fitness and transmissibility 73 .…”

Section: Na Inhibitors and Resistance Mutationsmentioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

208

216

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Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity and antigenic significance of neuraminidase.

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“…The first cases of oseltamivir-resistant pandemic H1N1/ 09 virus were identified in July 2009 (68). Oseltamivir resistance is conferred by the H275Y mutation (histidine to tyrosine, H274Y in N2 numbering) in the NA gene (69).…”

Section: Antiviral Drug Resistancementioning

confidence: 99%

Pandemic influenza A (H1N1) 2009: the experience of the first six months

Maritz

Maree²,

Preiser³

2009

Clinical Chemistry and Laboratory Medicine

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After a break of 41 years, 2009 saw the first influenza pandemic of the 21st century caused by a triple-reassortant influenza A (H1N1) virus. The current estimated case fatality rate is lower than that of previous influenza pandemics, but this may change as the pandemic evolves. Illness frequently occurs in previously healthy, young adults with a wide range of clinical presentations. The majority of circulating pandemic viruses remain susceptible to neuraminidase inhibitors, although all strains are intrinsically resistant to the adamantanes. Monovalent vaccines against the pandemic strain are available in both live attenuated and inactivated forms. This review aims to summarise important virological, epidemiological and clinical aspects of the pandemic influenza A (H1N1) virus for physicians and other clinical personnel. Clin Chem Lab Med 2010;48:11-21.

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The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo

Cited by 345 publications

References 21 publications

Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts

Comparative Pathology in Ferrets Infected with H1N1 Influenza A Viruses Isolated from Different Hosts

Influenza neuraminidase

Pandemic influenza A (H1N1) 2009: the experience of the first six months

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