RESUMEN
The differences in the influenza viral pathogenesis observed between different pathogenic strains are associated with distinct properties of virus strains and the host immune responses. In order to determine the differences in the duck immune response against two different pathogenic strains, we studied genome-wide host immune gene response of ducks infected with A/duck/India/02CA10/2011 and A/duck/Tripura/103597/2008 H5N1 viruses using custom-designed microarray. A/duck/India/02CA10/2011 is highly pathogenic virus (HP) to ducks, whereas A/duck/Tripura/103597/2008 is a low pathogenic (LP) virus strain. Comparative lung tissue transcriptome analysis of differentially expressed genes revealed that 686 genes were commonly expressed, 880 and 1556 genes are expressed uniquely to infection with HP and LP virus, respectively. The up-regulation of chemokines (CCL4 and CXCR4) and IFN-stimulated genes (IFITM2, STAT3, TGFB1 and TGFB3) was observed in the lung tissues of ducks infected with HP virus. The up-regulation of other immune genes (IL17, OAS, SOCS3, MHC I and MHC II) was observed in both infection conditions. The expression of important antiviral immune genes MX, IFIT5, IFITM5, ISG12, ß-defensins, RSAD2, EIF2AK2, TRIM23 and SLC16A3 was observed in LP virus infection, but not in HP virus infection. Several immune-related gene ontology terms and pathways activated by both the viruses were qualitatively similar but quantitatively different. Based on these findings, the differences in the host immune response might explain a part of the difference observed in the viral pathogenesis of high and low pathogenic influenza strains in ducks.
Asunto(s)
Patos , Regulación de la Expresión Génica/inmunología , Estudio de Asociación del Genoma Completo , Subtipo H5N1 del Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Animales , Análisis por Matrices de Proteínas , VirulenciaRESUMEN
The highly pathogenic avian influenza (HPAI) H5N1 virus, currently circulating in Asia, causes severe disease in domestic poultry as well as wild birds like crow. However, the molecular pathogenesis of HPAIV infection in crows and other wild birds is not well known. Thus, as a step to explore it, a comprehensive global gene expression analysis was performed on crow lungs, infected with HPAI H5N1 crow isolate (A/Crow/India/11TI11/2011) using high throughput next generation sequencing (NGS) (GS FLX Titanium XLR70). The reference genome of crow is not available, so RNA seq analysis was performed on the basis of a de novo assembled transcriptome. The RNA seq result shows, 4052 genes were expressed uniquely in noninfected, 6277 genes were expressed uniquely in HPAIV infected sample and of the 6814 genes expressed in both samples, 2279 genes were significantly differentially expressed. Our transcriptome profile data allows for the ability to understand the molecular mechanism behind the recent lethal HPAIV outbreak in crows which was, until recently, thought to cause lethal infections only in gallinaceous birds such as chickens, but not in wild birds. The pattern of differentially expressed genes suggest that this isolate of H5N1 virus evades the host innate immune response by attenuating interferon (IFN)-inducible signalling possibly by down regulating the signalling from type I IFN (IFNAR1 and IFNAR2) and type II IFN receptors, upregulation of the signalling inhibitors suppressor of cytokine signalling 1 (SOCS1) and SOCS3 and altering the expression of toll-like receptors (TLRs). This may be the reason for disease and mortality in crows.