Susceptibility of human H3N2 influenza virus to oseltamivir in South Korea, 2009–2011

Park, Sehee; Kim, Sang Hyun; Lee, Ilseob; Lee, Sang Moo; Hwang, Miriam; Bae, Jin‐Young; Heo, Jun; Lim, Eun Joo; Seok, Won Seok; Cheong, Hee Jin; Song, Joon Young; Park, Man Seong

doi:10.1007/s12275-012-2541-3

Cited by 6 publications

(6 citation statements)

References 14 publications

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“…As previously known with other 2009 pandemic H1N1 strains [34], the K/09 virus was sensitive to oseltamivir carboxylate and peramivir (5.07 nM IC 50 for oseltamivir carboxylate and 1.38 nM IC 50 for peramivir; Table 1). However, the recombinant K09/NA:Y275 virus, which was formerly used as an oseltamivir-resistant control harboring the H275Y mutation in the NA protein (Table S1) [32], circumvented the antiviral efficacy of both NAIs, resulting in more than 75-fold elevated IC 50 values compared with those of the K/09 virus (423.10 nM for oseltamivir carboxylate and 104.40 nM for peramivir; Table 1). The K/2785 virus which retaining the NA H275Y mutation was also resistant to NAIs and needed more than 20-fold higher concentrations (238 nM for oseltamivir carboxylate and 29.76 nM for peramivir) of NAIs to be controlled compared with the K/09 virus (Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

et al. 2014

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Antiviral drugs are being used for therapeutic purposes against influenza illness in humans. However, antiviral-resistant variants often nullify the effectiveness of antivirals. Combined medications, as seen in the treatment of cancers and other infectious diseases, have been suggested as an option for the control of antiviral-resistant influenza viruses. Here, we evaluated the therapeutic value of combination therapy against oseltamivir-resistant 2009 pandemic influenza H1N1 virus infection in DBA/2 mice. Mice were treated for five days with favipiravir and peramivir starting 4 hours after lethal challenge. Compared with either monotherapy, combination therapy saved more mice from viral lethality and resulted in increased antiviral efficacy in the lungs of infected mice. Furthermore, the synergism between the two antivirals, which was consistent with the survival outcomes of combination therapy, indicated that favipiravir could serve as a critical agent of combination therapy for the control of oseltamivir-resistant strains. Our results provide new insight into the feasibility of favipiravir in combination therapy against oseltamivir-resistant influenza virus infection.

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Section: Resultsmentioning

confidence: 99%

“…Reverse transcriptase-PCR and subsequent sequence analysis confirmed the NA H275Y mutation in the K/2785 virus, which confers resistance to oseltamivir. The rK09/NA:Y275 virus (see Table S1 for NA gene sequence information), which was previously rescued by plasmid-based reverse genetics [32], was also used as an oseltamivir-resistant control.…”

Section: Methodsmentioning

confidence: 99%

Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

et al. 2014

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“…Low vaccine effectiveness has also been observed, however, based on the genetic mutation of the virus with seven substitutions at key antigenic sites 23. The mutation in H3N2 virus has also been responsible for oseltamivir resistance that was observed in patients between 2009 and 2011 8. Recently, a new blood assay has been developed for early detection of influenza A (H1N1 and H3N2), which can be applied in the emergency department of hospitals and could be a future methodology for early influenza detection 42.…”

Section: Discussionmentioning

confidence: 99%

“…In an effort to achieve efficient surveillance of H1N1, a network was proposed and established by several countries 7. During the first pandemic of H1N1 influenza, H3N2 cases were also isolated 8. The laboratory methods for identifying the different antigens of the influenza family have been reported, and they are very useful in identifying H1N1 from H3N2 9,10.…”

Section: Introductionmentioning

confidence: 99%

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Clinical differences between H3N2 and H1N1 influenza 2012 and lower respiratory tract infection found using a statistical classification approach

Petridis¹,

Kallianos²,

Kioumis³

et al. 2014

TCRM

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BackgroundInfluenza A H1N1 and H3N2 are two influenza waves that have been identified in past years.MethodsData from 77 inpatients from three tertiary hospitals were included and statistical analysis was performed in three different clusters.ResultsThirty-four patients (44.2%) had respiratory distress upon admission, 31.2% had a smoking history or were active smokers, 37.7% manifested disease symptoms, and 7.8% were obese (body mass index >41). The mean age of patients was 51.1 years. Cough was the most common symptom observed in 77.9% of the patients, accompanied by sputum production (51.9%) and fatigue (42.9%). Hemoptysis and vomiting were rarely recorded in the patients (9.1% and 16.9%, respectively). Oseltamivir administration varied between 0 and 10 days, giving a mean value of 2.2 days. In particular, 19 patients received no drug, 31 patients received drug for only for 1 day, 19 patients for 5 days, and 8 patients from 2 to 10 days.ConclusionClusters of symptoms can be used to identify different types of influenza and disease severity. Patients with vaccination had pneumonia, whereas patients without vaccination had influenza A. Patients more than 54.5 years old had H3N2 and patients less than 54.5 years had H1N1. White blood cell count values increased from normal to elevated in H3N2 patients but still remained abnormal in lower tract infection and H1N1 patients.

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Effects of a hemagglutinin D222G substitution on the pathogenicity of 2009 influenza A (H1N1) virus in mice

et al. 2014

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The surface glycoprotein hemagglutinin (HA) of influenza virus initiates the infection process by binding to sialic acid receptors on upper respiratory cells in the host. In contrast to avian influenza viruses, which bind to sialic acids connected by an α2-3 linkage to the penultimate galactose, human influenza viruses prefer sialic acids with an α2-6 linkage. Recently, there have been multiple cases of severe human infections associated with an HA D222G mutant influenza virus. In this study, we have investigated the pathogenic effects of the HA D222G substitution in a 2009 pandemic H1N1 virus in mice. Compared with the A/Korea/01/2009 (K/09) virus, the HA D222G mutant showed reduced growth in cells and reduced binding avidity to human and turkey red blood cells. In a BALB/c mouse infection model, infection with the HA D222G mutant virus resulted in less body weight loss when compared to the parental K/09 virus. Altogether, our data suggest that the HA D222G substitution in the K/09 virus might be deleterious to viral fitness.

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Susceptibility of human H3N2 influenza virus to oseltamivir in South Korea, 2009–2011

Cited by 6 publications

References 14 publications

Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

Combination Effects of Peramivir and Favipiravir against Oseltamivir-Resistant 2009 Pandemic Influenza A(H1N1) Infection in Mice

Clinical differences between H3N2 and H1N1 influenza 2012 and lower respiratory tract infection found using a statistical classification approach

Effects of a hemagglutinin D222G substitution on the pathogenicity of 2009 influenza A (H1N1) virus in mice

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