Outbreaks of avian influenza A (H5N1) virus, a highly pathogenic avian influenza (HPAI), are considered as a public health risk with pandemic potential . Understanding the pathology, transmission, clinical features and treatments has become necessary for the prevention and management of such outbreaks [2, 3]. The mechanisms responsible for the virulence of HPAI viruses in humans are not completely understood. Viral factors are necessary for productive infection but are not sufficient to explain the pathogenesis of HPAI infection in humans [4, 5].
It is well recognized that host immunological and genetic factors also play an important role in the pathogenesis of H5N1 viruses in humans [5, 6]. Recent studies have shown that the high fatality rate of avian influenza virus infections is a consequence of the complex interaction of virus and host immune responses which include overactive inflammatory response in the form of hypercytokinemia (cytokine storm), that is initiated inside the infected cells or tissue in response to virus replication resulting in excessive cellular apoptosis and tissue damage [7–9]. In vitro, in vivo and clinical studies have suggested that H5N1 viruses are very strong inducers of various cytokines and chemokines [Tumor Necrosis Factor (TNF)-alpha, Interferon (IFN)-gamma, IFN-alpha/beta, Interleukin (IL)-6, IL-1, MIP-1 (Macrophage Inflammatory Protein), MIG (Monokine Induced by IFN-gamma), IP-10 (Interferon-gamma-Inducible Protein), MCP-1 (Monocyte Chemoattractant Protein), RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), IL-8], in both humans and animals [10–12]. However, it has also been reported that preventing cytokine response doesn't prevent H5N1 infection and cell death . Hence, further studies are needed to understand the pathogenesis of H5N1 virus infection.
Alveolar epithelial cells and macrophages are the key targets for H5N1 virus in the lungs . Using infection in human lung carcinoma cells we analyzed early and late host responses at 4, 8, 16 and 24 hours post infection by employing gene expression profiling on a microarray platform. A comparative analysis was thus carried out at different time points post infection between highly pathogenic avian influenza A H5N1 virus (HPAI-H5N1), A/Chicken/India/WB-NIV2664/2008(H5N1) and modified recombinant vaccine virus (RG modified H5N1), A/India/NIV/2006(H5N1)-PR8-IBCDC-RG7.
A/Chicken/India/WB-NIV2664/2008 is a recent strain of H5N1 of clade 2.2 circulating in chicken population in India  and A/India/NIV/2006(H5N1)-PR8-IBCDC-RG7 is a reverse genetics modified virus generated from HPAI, A/chicken/India/NIV33487/2006 (H5N1) of the same clade . The objective was to understand the host responses at different stages of virus infection at cellular level, which could provide some insight into the biology of virus-host interaction leading to the explanation that how virus infection modulates host cellular environment in A549 cells.