Abstract
Low pathogenic avian influenza (LPAI) viruses are a source of sporadic human infections and could also contribute to future pandemic outbreaks but little is known about inter-species differences in the host responses to these viruses. Here, we studied host gene expression signatures of cell lines from three species (human, chicken, and canine) in response to six different viruses (H1N1/WSN, H5N2/F59, H5N2/F118, H5N2/F189, H5N3 and H9N2). Comprehensive microarray probe set re-annotation and ortholog mapping of the host genes was necessary to allow comparison over extended functionally annotated gene sets and orthologous pathways. The annotations are made available to the community for commonly used microarray chips. We observe a strong tendency of the response being cell type- rather than virus-specific. In chicken cells, we found up-regulation of host factors inducing virus infectivity (e.g., oxysterol binding protein like 1A (OSBPL1A) and Rho GTPase activating protein 21 (ARHGAP21)) while reducing apoptosis (e.g., mitochondrial ribosomal protein S27 (MRPS27)) and increasing cell proliferation (e.g., COP9 signalosome subunit 2 (COPS2)). On the other hand, increased antiviral, pro-apoptotic and inflammatory signatures have been identified in human cells while cell cycle and metabolic pathways were down-regulated. This signature describes how low pathogenic avian influenza (LPAI) viruses are being tolerated and shed from chicken but potentially causing cellular disruption in mammalian cells.
Highlights
Influenza A virus (IAV) is a zoonotic virus that is present in several animal reservoirs [1]
Madin-Darby canine kidney (MDCK) cells are highly permissive to IAV infection allowing propagation of clinical and veterinary strains of influenza virus. These cell types would be expected to exhibit transcription profiles that are distinct from the tissue they are derived, it would be expected that signaling networks that are present within these cells types would retain species-specific properties
We have previously described several low pathogenic avian influenza (LPAI) viruses H5N2, H5N3 and H9N2 that were isolated from live ducks that were imported into Singapore [9]
Summary
Influenza A virus (IAV) is a zoonotic virus that is present in several animal reservoirs (e.g., avian, pigs) [1]. MDCK cells are highly permissive to IAV infection allowing propagation of clinical and veterinary strains of influenza virus These cell types would be expected to exhibit transcription profiles that are distinct from the tissue they are derived, it would be expected that signaling networks (e.g., such as those related to the innate host response to infection) that are present within these cells types would retain species-specific properties (e.g., how they are regulated). Since these cells are highly permissive for influenza virus infection they would serve as good models to understand the cellular changes that IAVs induce that are pro-viral in nature. The data suggested the expression changes in IAV infection are in the order of MDCK > A549 > CEF with exceptions of up-regulated genes in A549 vs. MDCK and the H5N2/F118 virus infection in A549 vs. CEF cells
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