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Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
H1N1 influenza A virus neuraminidase modulates infectivity in mice
Olivier Ferraris1, Vanessa Escuret, Maude Bouscambert
1Université de Lyon, F-69000 Lyon, France.
Abstract:
In the 2years since the onset of the H1N1 2009 pandemic virus (H1N1pdm09), sporadic cases of oseltamivir-resistant viruses have been reported. We investigated the impact of oseltamivir-resistant neuraminidase from H1N1 Brisbane-like (seasonal) and H1N1pdm09 viruses on viral pathogenicity in mice. Reassortant viruses with the neuraminidase from seasonal H1N1 virus were obtained by co-infection of a H1N1pdm09 virus and an oseltamivir-resistant H1N1 Brisbane-like virus. Oseltamivir-resistant H1N1pdm09 viruses were also isolated from patients. After biochemical characterization, the pathogenicity of these viruses was assessed in a murine model. We confirmed a higher infectivity, in mice, of the H1N1pdm09 virus compared to seasonal viruses. Surprisingly, the oseltamivir-resistant H1N1pdm09 virus was more infectious than its sensitive counterpart. Moreover, the association of H1N1pdm09 hemagglutinin and an oseltamivir-resistant neuraminidase improved the infectivity of reassortant viruses in mice, regardless of the NA origin: seasonal (Brisbane-like) or pandemic strain. This study highlights the need to closely monitor the emergence of oseltamivir-resistant viruses.
Insights
Oseltamivir-resistant H1N1pdm09 viruses showed increased infectivity in mice. The pandemic virus
Area of Science:
- Virology
- Infectious Diseases
- Antiviral Resistance
Background:
- Sporadic cases of oseltamivir-resistant H1N1 2009 pandemic virus (H1N1pdm09) have emerged.
- Neuraminidase (NA) is a key target for influenza antiviral drugs like oseltamivir.
- Understanding the pathogenicity of resistant strains is crucial for public health.
Purpose of the Study:
- To investigate the impact of oseltamivir-resistant neuraminidase on H1N1pdm09 pathogenicity in a murine model.
- To compare the infectivity of oseltamivir-resistant and sensitive H1N1pdm09 viruses.
- To assess the role of H1N1pdm09 hemagglutinin (HA) in conjunction with resistant NA.
Main Methods:
- Generation of reassortant viruses using H1N1pdm09 and oseltamivir-resistant seasonal H1N1 (Brisbane-like) viruses.
- Isolation of oseltamivir-resistant H1N1pdm09 viruses from patients.
- Biochemical characterization and pathogenicity assessment in a mouse model.
Main Results:
- H1N1pdm09 virus demonstrated higher infectivity in mice compared to seasonal H1N1.
- Oseltamivir-resistant H1N1pdm09 virus exhibited greater infectivity than its sensitive counterpart.
- Reassortant viruses with H1N1pdm09 HA and oseltamivir-resistant NA showed enhanced infectivity.
Conclusions:
- Oseltamivir resistance in H1N1pdm09 does not necessarily diminish viral pathogenicity.
- The H1N1pdm09 HA in combination with resistant NA enhances viral infectivity.
- Close monitoring for the emergence and spread of oseltamivir-resistant H1N1pdm09 is essential.
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