Non structural protein of avian influenza A (H11N1) virus is a weaker suppressor of immune responses but capable of inducing apoptosis in host cells

Sanjay Mukherjee,Akhilesh C Mishra,Shamik Majumdar,Veena C Vipat,Alok K Chakrabarti

doi:10.1186/1743-422x-9-149

Sanjay Mukherjee, Akhilesh C Mishra + Show 3 more

Open Access

https://doi.org/10.1186/1743-422x-9-149

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Journal: Virology journal	Publication Date: Aug 6, 2012
Citations: 31	License type: cc-by

Affiliation: ICMR-National Institute of Virology

Abstract

BackgroundThe Non-Structural (NS1) protein of Influenza A viruses is an extensively studied multifunctional protein which is commonly considered as key viral component to fight against host immune responses. Even though there has been a lot of studies on the involvement of NS1 protein in host immune responses there are still ambiguities regarding its role in apoptosis in infected cells. Interactions of NS1 protein with host factors, role of NS1 protein in regulating cellular responses and apoptosis are quite complicated and further studies are still needed to understand it completely.ResultsNS1 genes of influenza A/Chicken/India/WBNIV2653/2008 (H5N1) and A/Aquatic bird/India/NIV-17095/2007(H11N1) were cloned and expressed in human embryonic kidney (293T) cells. Microarray based approach to study the host cellular responses to NS1 protein of the two influenza A viruses of different pathogenicity showed significant differences in the host gene expression profile. NS1 protein of H5N1 resulted in suppression of IFN-β mediated innate immune responses, leading to down-regulation of the components of JAK-STAT pathway like STAT1 which further suppressed the expression of pro-inflammatory cytokines like CXCL10 and CCL5. The degree of suppression of host immune genes was found considerable with NS1 protein of H11N1 but was not as prominent as with H5N1-NS1. TUNEL assay analyses were found to be positive in both the NS1 transfected cells indicating both H5N1 as well as H11N1 NS1 proteins were able to induce apoptosis in transfected cells.ConclusionsWe propose that NS1 protein of both H5N1 and H11N1 subtypes of influenza viruses are capable of influencing host immune responses and possess necessary functionality to support apoptosis in host cells. H11N1, a low pathogenic virus without any proven evidence to infect mammals, contains a highly potential NS1 gene which might contribute to greater virus virulence in different gene combinations.

Highlights

The genome of influenza A viruses consists of eight segmented single stranded RNA with negative polarity which are capable of encoding a total of eleven known proteins [1]
Host gene expression responses to influenza A NS1: Comparison between NS1 protein of highly pathogenic H5N1 and low pathogenic H11N1 viruses We examined global cellular gene expression levels in cells transfected with NS1 gene of two avian influenza viruses (H5N1 and H11N1) and compared them with untransfected control cells and the cells transfected with the vector DNA only
Cells which were transfected with H5N1-NS1 construct showed significant changes in expression of 34 genes whereas cells transfected with H11N1-NS1 construct showed differential expression of Results In order to understand whether NS1 protein from Influenza A viruses of widely varied pathogenicity have different ability to modulate host responses, a comparative analysis of host gene expression profile was carried out in transfected cells using microarray experiments

Summary

Introduction

The genome of influenza A viruses consists of eight segmented single stranded RNA with negative polarity which are capable of encoding a total of eleven known proteins [1]. The eighth and the smallest RNA segment encodes for the nonstructural protein NS1, which plays a significant role in overcoming host cellular defense mechanism and establishment of a productive infection [2]. It has been shown by many investigators that multifunctional NS1 protein is a specificity factor). Inhibition of apoptosis, on the other hand was shown to happen through the activation of Phosphoinositide 3-kinase (PI3K) signaling pathway [15] These observations clearly indicate that the role of Influenza A NS1 protein in host cells is very complex and needs further studies. Interactions of NS1 protein with host factors, role of NS1 protein in regulating cellular responses and apoptosis are quite complicated and further studies are still needed to understand it completely

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