Abstract
Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. In this study, we characterized the immune and pathological progression of a seasonal strain of H1N1 influenza virus, A/Brisbane/59/2007 in a ferret model. The immune response of the animals showed a dose-dependent increase with increased virus challenge, as indicated by the presence of virus specific IgG, IgM, and neutralizing antibodies. Animals infected with higher doses of virus also experienced increasing severity of clinical symptoms and fever at 2 days post-infection (DPI). Interestingly, weight loss was more pronounced in animals infected with lower doses of virus compared to those infected with a higher dose; these results were consistent with viral titers of swabs collected from the nares, but not the throat. Analyzed specimens included nasal and throat swabs from 1, 3, 5, and 7 DPI as well as tissue samples from caudal lung and nasal turbinates. Viral titers of the swab samples in all groups were higher on 1 and 3 DPI and returned to baseline levels by 7 DPI. Analysis of nasal turbinates indicated presence of virus at 3 DPI in all infected groups, whereas virus was only detected in the lungs of animals in the two highest dose groups. Histological analysis of the lungs showed a range of pathology, such as chronic inflammation and bronchial epithelial hypertrophy. The results provided here offer important endpoints for preclinical testing of the efficacy of new antiviral compounds and experimental vaccines.
Highlights
Every year, influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications
Every year, influenza virus infects 5-20% of the US population with numerous deaths attributed to primary influenza infection or secondary bacterial pneumonia [1]
The rapid evolution of new influenza virus strains and drug resistant variants demands constant development of treatments as well as reliable animal models allowing for testing of these remedies [2,3]
Summary
Influenza viruses infect approximately 5-20% of the population in the United States leading to over 200,000 hospitalizations and 36,000 deaths from flu-related complications. A number of animal models are used for influenza research, ferrets are ideal because they can be readily infected with human isolates of influenza virus (in contrast to mice) and exhibit symptoms similar to humans, such as fever, coughing, sneezing, runny nose, lethargy [4,5,6,7,8,9,10], and make a full recovery in 7-10 days [11,12]. Five groups were challenged intranasally with increasing doses of A/Brisbane/59/2007, and controls received PBS.
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