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. 2010 Jul 9;7:149.
doi: 10.1186/1743-422X-7-149.

Course of Seasonal Influenza A/Brisbane/59/07 H1N1 Infection in the Ferret

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Free PMC article

Course of Seasonal Influenza A/Brisbane/59/07 H1N1 Infection in the Ferret

Alexis McBrayer et al. Virol J. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Clinical Pathology of A/Brisbane/59/2007 infected ferrets. (A) Control lung tissue; (B) Lung from ferret challenged with 103.8 EID50/ml with chronic inflammation in the bronchial glands; (C). Lung from ferret challenged with 104.8 EID50/ml with bronchiolar epithelial hypertrophy (white arrow) and, neutrophils and macrophages within alveoli and airways (black arrow); (D). Lung of ferret challenged with 106.8 EID50/ml with a syncytium within an alveolus (see blue arrow). Images were taken at 400x magnification
Figure 2
Figure 2
TCID50 Virus Titration Analysis. Blue dots indicate the titer of individual animals, the red line indicates the average for the animals tested in each group and day. For the caudal lung and nasal turbinates (A), four animals per group were analyzed at 3 DPI. In (B), analysis of throat and nasal swabs isolated at 1, 3, 5, and 7 DPI is shown. Eight samples per group were analyzed on 1 and 3 DPI, and four samples per group were analyzed on days 5 and 7 due to the euthanasia of 50% of the animals on 3 DPI.
Figure 3
Figure 3
Humoral and Cellular Immunity. (A and B) ELISA data show an increase in influenza specific IgM and IgG at 7 DPI compared to mock-infected control animals. These data show that there is a dose-dependent increase in antibody response. Bars indicate the average difference per group between log2-transformed end-point dilutions from pre-infection serum and post-infection serum. (C) Neutralization titer analysis was performed in order to detect the presence of influenza-specific neutralizing antibodies in the serum. The presence of neutralizing antibodies was measured only on 7 DPI. No neutralizing antibodies were detected in the sera from control animals. Only 2 out of 4 animals from group 2 and 1 out of 4 animals from group 3 had detectable neutralizing antibodies, while all animals in groups 4, 5, and 6 had detectable neutralizing antibodies. (D, E, and F) The number of neutrophils and lymphocytes, as well as the total number of white blood cells, increased in animals infected with A/Brisbane/59/07 compared to mock infected control animals. Y axis indicates number of cells as 103 cells per mm3.

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