Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice

Abstract

Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. In this study, selected 2009 A(H1N1) influenza isolates were assessed for their ability to cause disease in mice and ferrets and compared with a contemporary seasonal H1N1 virus for their ability to transmit to naïve ferrets through respiratory droplets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) influenza viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) influenza viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison with the highly transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) influenza viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) by use of dose-dependent direct receptor-binding and human lung tissue-binding assays.

Pandemic influenza A (H1N1) 2009: the experience of the first six months

“…Ferrets inoculated with pandemic H1N1/09 virus displayed more severe symptoms, involving the entire respiratory tract, compared with ferrets inoculated with seasonal influenza A (H1N1) which displayed symptoms of necrotising rhinitis only (17). The detection of pandemic H1N1/09 virus in the intestinal tract of some infected ferrets is consistent with the gastrointestinal complaints from several human patients with pandemic H1N1/09 infection (16).…”

“…Pandemic H1N1/09 virus pathogenicity and transmissibility studies conducted in ferrets, mice and cynomolgus macaques proved that the pandemic strain is more pathogenic than seasonal H1N1 influenza, as the virus replicated more efficiently in the lungs of all three animal models (15)(16)(17). Macaque lungs demonstrated severe thickening of the alveolar walls, and the alveolar spaces were filled with inflammatory infiltrates and oedematous exudates.…”

“…Two of the studies found that it spreads as efficiently as seasonal influenza A (H1N1) via aerosols and respiratory droplets (15,17). However, one study found that pandemic H1N1/09 virus is transmitted less efficiently via respiratory droplets (16). Droplet transmission does appear to be effective in humans, as an outbreak of pandemic H1N1/09 among tourists in China was caused by talking with the index patient at close range (18).…”

2009 pandemic Influenza A (H1N1): clinical and laboratory characteristics in pediatric and adult patients and in patients with pulmonary involvement

“…Vomiting/nausea and diarrhea were reported to be more prevalent in 2009 influenza A (H1N1) epidemic than in seasonal influenza ones 9 , 23 . In an animal experimental model, the pandemic 2009 influenza A (H1N1) virus was recovered from the gastrointestinal tract of the intranasally inoculated ferrets 24 . Isolation of the 2009 influenza A (H1N1) viruses from the human gastrointestinal tissue 25 and prolonged viral shedding from respiratory tract in younger children were previously reported 26 .…”

Factors promoting the prolonged shedding of the pandemic (H1N1) 2009 influenza virus in patients treated with oseltamivir for 5 days

“…With regard to the 2009 H1N1 influenza strain, the World Health Organization (WHO) has recommended that patients receive 5 days of treatment with antiviral agents 4. However, animal models show that the 2009 H1N1 virus replicates more efficiently than seasonal influenza viruses in the respiratory tract 5, 6, 7. In addition, several studies have shown that the 2009 H1N1 virus can still be present for 8 days or more 8, 9, 10, 11, 12.…”