Abstract
Influenza B virus (IBV) is a respiratory pathogen that infects humans and causes seasonal influenza epidemics. However, cellular response to IBV infection in humans and mechanisms of host-mediated restriction of IBV replication are not thoroughly understood. In this study, we used next-generation sequencing (NGS) to perform transcriptome profiling of IBV-infected human lung epithelial A549 cells at 0, 6, 12, and 24 h post infection (hpi) and characterized the cellular gene expression dynamics. We observed that more than 4000 host genes were differentially regulated during the study period, which included up regulation of genes encoding proteins, having a role in the innate antiviral immune responses, immune activation, cellular metabolism, autophagy, and apoptosis, as well as down regulation of genes involved in mitosis and cell proliferation. Further analysis of RNA-Seq data coupled with RT-qPCR validation collectively showed that double-strand RNA recognition pathways, including retinoic acid-inducible gene I (RIG-I) and Toll-like receptor 3 (TLR3), were substantially activated following IBV infection. Taken together, these results provide important initial insights into the intimate interaction between IBV and lung epithelial cells, which can be further explored towards elucidation of the cellular mechanisms in restriction or elimination of IBV infections in humans.
Highlights
Influenza viruses are classified as types A, B, and C according to their distinct antigenic properties residing in two major structural proteins [1]
The principle component analysis showed that the cellular transcriptome profiles of duplicates were highly similar but diverged between time points, suggesting that Influenza B virus (IBV) infection affected gene expression profiles of the host, which had been reported in our previous work [32]
We examined IBV infection induced response in human lung epithelial
Summary
Influenza viruses are classified as types A, B, and C according to their distinct antigenic properties residing in two major structural proteins (matrix 1 and nucleocapsid) [1]. A new type of influenza virus with bovine as a primary reservoir, officially designated influenza type D, has been described [2,3]. Among these influenza viruses, only influenza A and B viruses (IAV and IBV) are of medical importance. It has been well established that humans are the primary host and reservoir of IBV [4,5,6,7], sporadic infection episodes of IBVs have been described in seals and pigs [8,9]. IBV infection of humans can result in the same spectrum of clinical disease as IAV, ranging from mild to severe respiratory illness requiring immediate hospitalization and medical treatment [7,10]
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