Reduced airborne transmission of oseltamivir-resistant pandemic A/H1N1 virus in ferrets

Antivir Ther. 2011;16(5):775-9. doi: 10.3851/IMP1794.


Background: The H275Y neuraminidase mutation conferring oseltamivir resistance has been reported in several pandemic A/H1N1 (pH1N1) isolates. We sought to evaluate transmission of this mutant virus through the direct contact and the airborne (aerosol and droplet) routes in the ferret model.

Methods: Groups of four ferrets were infected with either wild-type (WT) or oseltamivir-resistant pH1N1 (H275Y) strains. At 24 h following viral infection, a receptive ferret was introduced in the same cage as the infected animal to assess direct contact transmission. For the airborne transmission, naive ferrets were placed in a modified separate cage adjacent to that of their respective index ferret.

Results: The H275Y mutant virus was as efficiently transmitted as the WT strain by direct contact, as 100% (4/4) of contact ferrets in both groups seroconverted and shed virus. Mean peak viral titres were similar in both groups (4 × 10(4) and 2.63 × 10(4) plaque-forming units/ml after WT or H275Y mutant virus transmission, respectively). Peak viral shedding occurred on day 2 post-contact for the WT group and on day 4 post-contact for the H275Y mutant group. By contrast, airborne transmission of the mutant strain was less efficient, as only 25% (1/4) of contact ferrets seroconverted and shed virus, whereas 100% (4/4) of the WT ferrets did. Peak of viral replication was delayed compared to direct contact transmission and occurred on day 4 post-contact.

Conclusions: Transmission of the H275Y pH1N1 mutant strain by the airborne route is somewhat compromised, which may limit its widespread dissemination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Air Microbiology
  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Disease Models, Animal
  • Disease Transmission, Infectious / prevention & control
  • Drug Resistance, Viral / genetics*
  • Ferrets
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / isolation & purification
  • Male
  • Neuraminidase / genetics
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / epidemiology
  • Orthomyxoviridae Infections / genetics
  • Orthomyxoviridae Infections / transmission*
  • Oseltamivir / pharmacology
  • Oseltamivir / therapeutic use*
  • Pandemics*
  • Time Factors
  • Viral Load
  • Virus Replication / drug effects*
  • Virus Replication / genetics


  • Antiviral Agents
  • Oseltamivir
  • Neuraminidase