A System Based-Approach to Examine Host Response during Infection with Influenza A Virus Subtype H7N9 in Human and Avian Cells.

Biruhalem Taye,Dawn Su-Yin Yeo,Michelle Su-Yen Wong,Hui Chen,Boon-Huan Tan,Richard J Sugrue,Shirley Gek-Kheng Seah

doi:10.3390/cells9020448

Abstract

Although the influenza A virus H7N9 subtype circulates within several avian species, it can also infect humans with a severe disease outcome. To better understand the biology of the H7N9 virus we examined the host response to infection in avian and human cells. In this study we used the A/Anhui/1/2013 strain, which was isolated during the first wave of the H7N9 epidemic. The H7N9 virus-infected both human (Airway Epithelial cells) and avian (Chick Embryo Fibroblast) cells, and each infected host transcriptome was examined with bioinformatic tools and compared with other representative avian and human influenza A virus subtypes. The H7N9 virus induced higher expression changes (differentially regulated genes) in both cell lines, with more prominent changes observed in avian cells. Ortholog mapping of differentially expression genes identified significant enriched common and cell-type pathways during H7N9 infections. This data confirmed our previous findings that different influenza A virus subtypes have virus-specific replication characteristics and anti-virus signaling in human and avian cells. In addition, we reported for the first time, the new HIPPO signaling pathway in avian cells, which we hypothesized to play a vital role to maintain the antiviral state of H7N9 virus-infected avian cells. This could explain the absence of disease symptoms in avian species that tested positive for the presence of H7N9 virus.

Highlights

Influenza viruses are an important cause of respiratory infection, and the global disease burden for influenza infections is estimated by the World Health Organisation to be responsible for up to 650,000 deaths annually
A549 and chick embryo fibroblast (CEF) cells were infected with influenza A virus subtype H7N9 using an multiplicity of infection (MOI) of 5 and at 2, 4, 6, 8, and 10 hpi the virus-infected cells were stained with anti-NP and examined by immunofluorescence (IF) microscopy (Figure 1A,B)
At 10 hpi anti-NP staining was observed in both the nucleus area and the cytoplasm, and the staining was consistent with efficient nuclear export of the RNP complexes in both A549 and CEF cells infected with the H7N9 virus

Summary

Introduction

Influenza viruses are an important cause of respiratory infection, and the global disease burden for influenza infections is estimated by the World Health Organisation to be responsible for up to 650,000 deaths annually (http://www.who.int/mediacentre/news/releases/2017/seasonal-flu/en/). In the context of human infections, many regions of the world experience seasonal epidemics involving increased human-to-human transmission of influenza virus and disease burden. It was originally thought that the transmission of avian influenza virus to humans could only occur via an interspecies host (e.g., swine), avian influenza viruses (e.g., H5N1) can be transmitted directly from birds to humans. Such events are usually self-limiting, since these viruses do not adapt to efficiently replicate in a mammalian host, and they do not exhibit efficient human-to-human transmission. In a relatively small time-scale, new virus variants can be potentially generated, and these two processes have been the basis for past influenza virus pandemics [5,6,7]

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