Antiviral Responses by Swine Primary Bronchoepithelial Cells Are Limited Compared to Human Bronchoepithelial Cells Following Influenza Virus Infection

Mary J Hauser,Daniel Dlugolenski,David E Wentworth,Marie R Culhane,Ralph A Tripp,S Mark Tompkins,Michael Cw Chan

doi:10.1371/journal.pone.0070251

Abstract

Swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. Type I and III interferons (IFNs) act as the first line of defense against influenza virus infection of respiratory epithelium. To determine if human and swine have different capacities to mount an antiviral response the expression of IFN and IFN-stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and normal swine bronchial epithelial (NSBE) cells was evaluated following infection with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A viruses. Expression of IFNλ and ISGs were substantially higher in NHBE cells compared to NSBE cells following H5 avian influenza virus infection compared to human or swine influenza virus infection. This effect was associated with reduced H5 avian influenza virus replication in human cells at late times post infection. Further, RIG-I expression was lower in NSBE cells compared to NHBE cells suggesting reduced virus sensing. Together, these studies identify key differences in the antiviral response between human and swine respiratory epithelium alluding to differences that may govern influenza reassortment.

Highlights

Influenza viruses pose a significant risk to human health due to their continuous evolution and zoonotic potential
The highly pathogenic H5N1 avian influenza virus has recently crossed the species barrier to infect humans resulting in a high mortality rate, and reassortant viruses with internal genes of avian H5 lineage have been identified in swine, raising concern about the pandemic potential of reassortant H5 viruses [7,8]
Both normal human bronchial epithelial (NHBE) and normal swine bronchial epithelial (NSBE) differentiated cells displayed predominantly α-2,6 linked sialic acid expression which is consistent with a previous finding that showed that α-2,6 linked sialic acid was the predominant receptor in all areas of the swine respiratory tract (16)

Summary

Introduction

Influenza viruses pose a significant risk to human health due to their continuous evolution and zoonotic potential. The segmented nature of the influenza viral genome allows for reassortment among virus strains which is a factor in virus adaptation [2]. The influenza pandemic of 1918 resulted in the deaths of 50 million people and based on analysis using Bayesian relaxed clock methods the virus was generated by reassortment between avian viruses and previously circulating human and swine strains over a period of years [4]. The highly pathogenic H5N1 avian influenza virus has recently crossed the species barrier to infect humans resulting in a high mortality rate, and reassortant viruses with internal genes of avian H5 lineage have been identified in swine, raising concern about the pandemic potential of reassortant H5 viruses [7,8]

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