Anti-H7N9 avian influenza A virus activity of interferon in pseudostratified human airway epithelium cell cultures

Ai-Jun Chen,Shu-Zhen Li,Hong Bo,Li-Shu Zheng,Chao Wang,Zhao-Jun Duan,Jie Dong,Xin-Hui Yuan

doi:10.1186/s12985-019-1146-4

Abstract

BackgroundSince H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. In preparation for a potential H7N9 epidemic, it is essential to evaluate the efficacy of anti-H7N9 drugs with an appropriate model.MethodsWell-differentiated pseudostratified human airway epithelium (HAE) cells were grown at the air–liquid interface, and the H7N9 cell tropism and cytopathic effect were detected by immunostaining and hematoxylin-eosin (HE) staining. The H7N9 replication kinetics and anti-H7N9 effect of recombinant human α2b (rhIFN-α2b) and rhIFN-λ1 were compared with different cell lines. The H7N9 viral load and interferon-stimulated gene (ISG) expression were quantified by real-time PCR assays.ResultsH7N9 could infect both ciliated and non-ciliated cells within the three-dimensional (3D) HAE cell culture, which reduced the number of cilia and damaged the airways. The H7N9 replication kinetics differed between traditional cells and 3D HAE cells. Interferon had antiviral activity against H7N9 and alleviated epithelial cell lesions; the antiviral activity of rhIFN-α2b was slightly better than that of rhIFN-λ1. In normal cells, rhIFN-α2b induced a greater amount of ISG expression (MX1, OAS1, IFITM3, and ISG15) compared with rhIFN-λ1, but in 3D HAE cells, this trend was reversed.ConclusionsBoth rhIFN-α2b and rhIFN-λ1 had antiviral activity against H7N9, and this protection was related to the induction of ISGs. The 3D cell culture model is suitable for evaluating interferon antiviral activity because it can demonstrate realistic in vivo-like effects.

Highlights

Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health
In contrast with the state of the cilia in the mock control, 3D human airway epithelium (HAE) cells that were infected with H7N9 showed an obvious reduction of cilia
The H7N9-infected 3D HAE cells showed a disassociation of the zonula occludens-1 (ZO-1), suggesting airway epithelial damage

Summary

Introduction

Since H7N9 influenza A virus (H7N9) was first reported in 2013, five waves of outbreaks have occurred, posing a huge threat to human health. Since the first human infection with a novel H7N9 influenza virus (H7N9) was confirmed in China in the spring of 2013 [1], there have been five epidemic waves of human H7N9 infections through 2017 [2]. There is currently no commercial human vaccine available that is specific for H7N9. Antiviral treatment is another critical strategy for controlling infection with H7N9, and neuraminidase (NA) inhibitors are the most widely used drugs against influenza infection [3]. With the increase in drug-resistance-conferring mutations, other measures are needed to treat infection with H7N9. The natural IFN Alferon N, was shown to inhibit the replication of oseltamivir-sensitive and -resistant H7N9 isolates [6]

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Discussion

Conclusion