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Institute of Virology

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Transmission of influenza A viruses in guinea pigs

Neuraminidase inhibitors such as oseltamivir and zanamivir are routinely used worldwide for the treatment of severe influenza A virus infection. Should drug-resistant viruses become widespread, this potent treatment strategy might fail. We address the question whether the resistance mutations in viral neuraminidase might reduce viral fitness by studying virus transmission in the guinea pig model.

Wild-type and oseltamivir-resistant pandemic H1N1 viruses are transmitted efficiently by physical contact in the guinea pig model.
The pandemic H1N1 isolate (A/HH/01/2009), its recombinant wild-type equivalent (rHH-wt) (B), and a H275Y NA-mutant (rHH-H275Y) (C) were transmitted from guinea pigs intranasally inoculated with 104 PFU to naïve guinea pigs exposed by physical contact, with transmission rates of 100%. (Figure from Seifert et al., 2010)

Open questions presently being investigated include:
a) Fitness of zanamivir-resistant pandemic H1N1 virus mutants

Selected Publications from our group

  1. Van Hoeven N, Belser JA, Szretter KJ, Staeheli P, Swayne DE, Katz JM, Tumpey TM. Pathogenesis of the 1918 pandemic and H5N1 influenza virus infection in a guinea pig model: the antiviral potential of exogenous alpha-interferon to reduce virus shedding. J. Virol. 83: 2851-2861 (2009)
  2. Steel J, Staeheli P, Mubareka S, García-Sastre A, Palese P, Lowen AC. Transmission of swine-origin influenza virus and impact of prior exposure to seasonal strains or interferon treatment. J. Virol. 84: 21-26 (2010)
  3. Seifert CW, Kaminski M, Philipp J, Rubbenstroth D, Albrecht RA, Schwalm F, Stertz S, Medina RA, Kochs G, Garcia-Sastre A, Staeheli P, Palese P. Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models. J Virol 84:11219-11226 (2010)
  4. Kaminski, M.M., Ohnemus, A., Staeheli, P., & D. Rubbenstroth. Pandemic 2009 H1N1 influenza A virus carrying a Q136K mutation in the neuraminidase gene is resistant to zanamivir but exhibits reduced fitness in the guinea pig transmission model. J. Virol. 87:1912-1915 (2013)

Collaboration

Prof. Peter Palese, Mount Sinai School of Medicine, New York
Dr. Mikhail Matrosovich, University of Marburg