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Abstract
BackgroundTo understand the molecular mechanism of host responses to highly pathogenic avian influenza virus infection and to get an insight into the means through which virus overcomes host defense mechanism, we studied global gene expression response of human lung carcinoma cells (A549) at early and late stages of infection with highly pathogenic avian Influenza A (H5N1) virus and compared it with a reverse genetics modified recombinant A (H5N1) vaccine virus using microarray platform.ResultsThe response was studied at time points 4, 8, 16 and 24 hours post infection (hpi). Gene ontology analysis revealed that the genes affected by both the viruses were qualitatively similar but quantitatively different. Significant differences were observed in the expression of genes involved in apoptosis and immune responses, specifically at 16 hpi.ConclusionWe conclude that subtle differences in the ability to induce specific host responses like apoptotic mechanism and immune responses make the highly pathogenic viruses more virulent.
Highlights
To understand the molecular mechanism of host responses to highly pathogenic avian influenza virus infection and to get an insight into the means through which virus overcomes host defense mechanism, we studied global gene expression response of human lung carcinoma cells (A549) at early and late stages of infection with highly pathogenic avian Influenza A (H5N1) virus and compared it with a reverse genetics modified recombinant A (H5N1) vaccine virus using microarray platform
Gene ontology analysis revealed that the genes involved in immune responses, translation and apoptosis were mostly up-regulated at all the time-points whereas genes involved in cell cycle and transcription were
Host gene expression response to RG modified H5N1 (IBCDC-RG7) virus infection The differentially expressed genes in cells infected with RG modified H5N1 (IBCDC-RG7) virus were involved in similar biological processes (GO analysis) as in response to H5N1 (WB-NIV2664) virus (Table 2)
Summary
To understand the molecular mechanism of host responses to highly pathogenic avian influenza virus infection and to get an insight into the means through which virus overcomes host defense mechanism, we studied global gene expression response of human lung carcinoma cells (A549) at early and late stages of infection with highly pathogenic avian Influenza A (H5N1) virus and compared it with a reverse genetics modified recombinant A (H5N1) vaccine virus using microarray platform. 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 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
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