Avian influenza virus H5N1 induces rapid interferon-beta production but shows more potent inhibition to retinoic acid-inducible gene I expression than H1N1 in vitro

Zhiqiang Mi,Yigang Tong,Yonghong Ma

doi:10.1186/1743-422x-9-145

Abstract

BackgroundThe mechanisms through which the avian influenza virus H5N1 modulate the host’s innate immune defense during invasion, remains incompletely understood. RIG-I as a pattern recognition receptor plays an important role in mediating innate immune response induced by influenza virus. So, modulating RIG-I might be adopted as a strategy by influenza virus to antagonize the host’s innate immune defense.MethodsHere we chose an avian influenza virus A/tree sparrow/Henan/1/04 (H5N1) directly isolated from a free-living tree sparrow in Mainland China which is amplified in egg allantoic cavity, and researched its interferon induction and manipulation of RIG-I expression compared with influenza virus A/WSN/1933(H1N1), a well characterized mouse adapted strain, in human lung epithelial A549 cells and human embryonic kidney 293T cells.ResultsAlthough the avian influenza virus H5N1 infection initiated a rapid IFN-beta production early on, it eventually presented a more potent inhibition to IFN-beta production than H1N1. Correspondingly, the H5N1 infection induced low level expression of endogenous RIG-I, an Interferon Stimulating Gene (ISG), and showed more potent inhibition to the expression of endogenous RIG-I triggered by exogenous interferon than H1N1.ConclusionsManipulating endogenous RIG-I expression might constitute one of the mechanisms through which avian influenza virus H5N1 control the host’s innate immune response during infection.

Highlights

The mechanisms through which the avian influenza virus H5N1 modulate the host’s innate immune defense during invasion, remains incompletely understood
Avian influenza virus A/tree sparrow/Henan/1/04 (H5N1) induces more rapid IFN-β production than human influenza virus H1N1 in early infection Innate immune response constitutes the first line of defense when a host encounters viral infections, but in the case of influenza virus infection, only low level or moderate IFN production is induced, and a different induction ability is apparent [14]
When normalized with multiplicity of infection, based on the level of nucleotide protein (NP) gene mRNA, we observed that the avian influenza virus A/tree sparrow/Henan/1/04(H5N1) infection was followed with more rapid and potent NP gene expression compared with human influenza virus H1N1 in the same multiplicity of infection (Figure 1A)

Summary

Introduction

The mechanisms through which the avian influenza virus H5N1 modulate the host’s innate immune defense during invasion, remains incompletely understood. RIG-I as a pattern recognition receptor plays an important role in mediating innate immune response induced by influenza virus. Modulating RIG-I might be adopted as a strategy by influenza virus to antagonize the host’s innate immune defense. Considering the important role of innate immune response in controlling virus transmission and pathogenesis [11,12], in the current study, a novel genotype H5N1 strain A/tree sparrow/Henan/1/04(H5N1) isolated from a tree sparrow in Mainland China was chosen [13] and its interferon-beta (IFN-β) induction and modulation of endogenous RIG-I expression were compared with human influenza virus H1N1 in human lung epithelial cells. Our results further approved that through manipulating innate immune response even the expression of RIG-I, avian influenza virus H5N1 struggle to control the host’s innate immune defense system for facilitating its invasion

Methods

Results

Conclusion