Modeling host responses in ferrets during A/California/07/2009 influenza infection

Abstract

Immune responses during infection with pandemic H1N1 2009 influenza A virus (2009-H1N1) are still poorly understood. Using an experimental infection model in ferrets, we examined the pathological features and characterized the host immune responses by using microarray analysis, during infection with 2009-H1N1 A/California/07/2009 and seasonal A/Brisbane/59/2007. Chemokines CCL2, CCL8, CXCL7 and CXCL10 along with the majority of interferon-stimulated genes were expressed early, correlated to lung pathology, and abruptly decreased expression on day 7 following infection of A/California/07/2009. Interestingly, the drop in innate immune gene expression was replaced by a significant increase of the adaptive immune genes for granzymes and immunoglobulins. Serum anti-influenza antibodies were first observed on day 7, commensurate with the viral clearance. We propose that lung pathology in humans occurs during the innate phase of host immunity and a delay or failure to switch to the adaptive phase may contribute to morbidity and mortality during severe 2009-H1N1 infections.

Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

“…Recently, a microarray analysis was reported characterizing host immune responses in ferret lung following infection with the pdmH1N1 (A/California/07/2009) and seasonal H1N1 (A/Brisbane/59/2007) [23]. In concordance with our study, they observed that IFN responses were triggered early after infection by both H1N1 viruses.…”

Next-generation sequencing and bioinformatic approaches to detect and analyze influenza virus in ferrets

“…Also, we found that the number of reads matching influenza sequences increased gradually from day 1 to day 5 after infection, and none was found on day 14 (Table 1). This trend correlates well with the viral titers that were previously observed in the lung tissue from which those samples were retrieved [23]. However, given the lack of biological replicates, we were unable to obtain any statistically significant conclusions regarding differences in the quantity of virus among the different experimental groups.…”

“…The number of short-reads mapped to influenza genes and the percentage of flu-matching reads per sample were as follows: day 1: 1,811 reads (0.005%), day 3: 9,580 reads (0.024%), day 5: 22,497 reads (0.056%) and on day 14 no influenza sequences were detected. The differences in the number of reads among time-points are in accordance with the evolution of the viral loads previously described for this infection model [23]. Finally, the pre-selected short-reads were processed with Iliad Assembler to generate the consensus sequence and to calculate the coverage percentage (Table 1).…”

“…After having performed different studies focused on the host immune responses during respiratory viral infections involving microarray analysis [23][24][25], our group decided to use RNA-seq to better characterize transcriptional variations during experimental influenza infections in ferrets. As part of this work, we also evaluated the presence of influenza virus in our samples.…”

Comparison of Temporal and Spatial Dynamics of Seasonal H3N2, Pandemic H1N1 and Highly Pathogenic avian influenza H5N1 Virus Infections in Ferrets

“…However, the location of virus replication and extent and severity of associated pathological changes were recorded at a single time point. Other experiments have used multiple time points (usually 1, 3, 5, and 14 dpi) to study the dynamics of influenza virus infection in the ferret respiratory tract [10,11,12,13,14,15,16]; however, these experiments often lacked detailed pathological or virological analyses of samples collected along the full length of the respiratory tract on all time points.…”