Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets

Abstract

The swine-origin A(H1N1) influenza virus that has emerged in humans in early 2009 has raised concerns about pandemic developments. In a ferret pathogenesis and transmission model, the 2009 A(H1N1) influenza virus was found to be more pathogenic than a seasonal A(H1N1) virus, with more extensive virus replication occurring in the respiratory tract. Replication of seasonal A(H1N1) virus was confined to the nasal cavity of ferrets, but the 2009 A(H1N1) influenza virus also replicated in the trachea, bronchi, and bronchioles. Virus shedding was more abundant from the upper respiratory tract for 2009 A(H1N1) influenza virus as compared with seasonal virus, and transmission via aerosol or respiratory droplets was equally efficient. These data suggest that the 2009 A(H1N1) influenza virus has the ability to persist in the human population, potentially with more severe clinical consequences.

Fig. 1

Weight loss and virus shedding in ferrets inoculated with seasonal and 2009 A(H1N1) influenza virus. Two groups of six ferrets each were inoculated intranasally with 10⁶ TCID₅₀ of virus. (A) Weight loss in inoculated animals is indicated as a percentage of body weight at the start of the experiment. Black squares indicate seasonal A(H1N1) and white squares indicate 2009 A(H1N1) influenza virus. (B) Virus shedding from the nose and throat of inoculated animals. Nose and throat swabs were collected daily, and virus titers in the swabs were determined by means of end-point titration in MDCK cells. Geometric mean titers are displayed; error bars indicate SD. Black bars indicate seasonal A(H1N1) and white bars indicate 2009 A(H1N1) influenza virus.

Fig. 2

Immunohistochemical analysis of respiratory tract tissues of ferrets inoculated with seasonal or 2009 A(H1N1) influenza virus, collected at 3 days after inoculation. Tissue sections of the nasal turbinates (A), trachea (B), and bronchi (C) were stained with a monoclonal antibody against influenza A virus nucleoprotein, which is visible as a red-brown staining. In animals inoculated with seasonal influenza virus, only cells in the nasal turbinates stained positive for nucleoprotein, whereas in animals inoculated with 2009 A(H1N1) influenza virus, cells in the nasal turbinates, trachea, and bronchi stained positive. See fig. S2 for data taken at 7 days after inoculation.