H1N1 influenza A virus neuraminidase modulates infectivity in mice

Olivier Ferraris1, Vanessa Escuret, Maude Bouscambert

  • 1Université de Lyon, F-69000 Lyon, France.

Antiviral Research
|February 11, 2012
PubMed

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.