title: Screening of differentially expressed transcripts in infectious bursal disease virus-induced apoptotic chicken embryonic fibroblasts by using cDNA microarrays.
abstract: Infectious bursal disease virus (IBDV) induces apoptosis and immunosuppression. To understand the molecular mechanisms involved in the pathogenesis of infectious bursal disease (IBD) and the host-directed antiviral responses, cDNA microarrays were used to identify the differentially expressed transcripts in IBDV-infected chicken embryonic fibroblasts. The results suggest a general suppression of surface receptors, including CD40 ligand and SEMA4D. These are related to T- and B-cell activation and differentiation, which may contribute to the immunosuppression of IBD. In addition, activation of genes involved in Toll-like receptor- and interferon (IFN)-mediated antiviral responses was detected. In particular, upregulation of Toll-like receptor 3, a double-stranded (ds) RNA receptor, and MX1, an IFN-inducible antiviral GTPase, may represent the possible host-directed defence responses against the virus and its dsRNA genome. Interestingly, several lines of evidence suggest the modulation of G protein-coupled receptors and receptor tyrosine kinase signalling pathways, especially the possible transactivation of epidermal growth factor receptor by lysophosphatidic acid. Alteration of these may contribute to the previously reported activation of mitogen-activated protein kinases upon IBDV infection, resulting in macrophage activation and inflammatory responses. Additionally, numerous target genes and inducers of nuclear factor kappa B (NF-kappaB) were upregulated profoundly, implying that IBDV may modulate host-cell survival and apoptosis to support its replication and facilitate viral spread through NF-kappaB activation. In summary, this investigation of host-gene expression unravelled the candidate physiological pathways involved in host-virus interaction on a molecular level, providing a foundation for researchers to design experiments based on testable hypotheses targeting individual genes.
authors.affiliation: Department of Zoology, The University of Hong Kong, Hong Kong SAR.
authors.forename: Raymond Tsz-Yeung
authors.initials: RT
authors.lastname: Wong
authors.affiliation: Department of Zoology, The University of Hong Kong, Hong Kong SAR.
authors.forename: Chung-Chau
authors.initials: CC
authors.lastname: Hon
authors.affiliation: Department of Zoology, The University of Hong Kong, Hong Kong SAR.
authors.forename: Fanya
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Department of Zoology, The University of Hong Kong, Hong Kong SAR.
authors.forename: Frederick C-C
authors.initials: FC
authors.lastname: Leung
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002642:Chick Embryo; D005347:Fibroblasts / Q000166:cytology / Q000821:virology*; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007243:Infectious bursal disease virus / Q000276:immunology* / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000096:biosynthesis / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016328:NF-kappa B; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; D019204:GTP-Binding Proteins