Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.3.23 (GAS)
 957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferons are essential for establishing cytotoxic T-lymphocyte immunity against viral pathogens through different mechanisms including the modulation of antigen presentation to T-cell subsets. At the present time, interferons have yet to be isolated from teleost fish. We have developed a salmonid model to examine whether MHC gene regulation is modulated during acute viral infection in trout, an event attributable to interferons in mammals. During peak infection with infectious hematopoietic necrosis virus, induction of STAT-1, PSMB9A and ABCB2 mRNA was evident in all tissues within infected fish, as compared with controls. In addition, MHC class Ia and beta(2) microglobulin (beta(2)m) transcript levels were enhanced within the experimental group but surprisingly, splenic and pronephric class IIB mRNA expression was virtually absent. A time-course study looking at 24, 72 and 192 h post-infection was then performed to determine the overall kinetics of this response. STAT-1 and PSMB9A message levels increased early during the immune response and remain at relatively high levels until the final time point. MHC class Ia expression is not consistently upregulated until midway in the response. MHC class IIB transcripts are downregulated by 72 h in the spleen and pronephros and then partially restored by 192 h. Finally, analysis of the putative promoter regions for PSMB9A and ABCB2 identified interferon (IFN) regulatory factory (IRF-1) and INF-gamma (GAS) activation sites that may be involved in the regulation of these genes during viral infection.
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PMID:Induction of the rainbow trout MHC class I pathway during acute IHNV infection. 1246 98

Infectious salmon anaemia virus (ISAV) is the causative agent of an important viral disease threatening Atlantic salmon aquaculture. Although its structure and pathogenesis is well described little is known about its immunomodulatory effects on the host. Cellular immunity is critical in the host control of virus infections, an event attributable to antigen presentation through the MHC class I pathway, whose genes are transcriptionally activated by interferons (IFN) and other cytokines. In this study we analysed the regulation and kinetics of key genes in the salmon MHC class I pathway in relation to type I IFN during ISAV infection and poly I:C stimulation in the permissive Atlantic salmon kidney cell line (ASK). As measured by quantitative real-time PCR, ISAV induced an mRNA shut-off equivalent to 2.5-5.5-fold reduced levels of housekeeping genes at 7 days post infection. Relative to this shut-off (by normalising to beta-actin) transcription increased to peak levels at 2.8-fold for MHC class I, 10-fold for beta 2 microglobulin (beta 2m), 5.9-fold for the peptide transporter ABCB2, 8.8-fold for the proteasome component PSMB8 and 4.6-fold for the proteasome component PSMB9, presumably by activation of the IFN system as a 26-fold induction was observed for type I IFN-alpha. Expression of Mx protein was also induced 17-fold at peak level. Similar kinetics and activation levels of these genes were seen in poly I:C stimulated cells. We also isolated the salmon MHC class I UBA*0301 promoter and identified a conserved interferon-stimulated response element (ISRE) and GAAA-elements plus several GAS- and IRF-sites, all supporting IFN-inducible properties. In summary, we demonstrate a concerted induction of the MHC class I pathway and type I IFN by ISAV comparable to levels induced by the synthetic double-stranded RNA (dsRNA) poly I:C. Thus, unlike influenza and several other viruses ISAV does not seem to interfere with MHC and IFN expression.
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PMID:Expression of MHC class I pathway genes in response to infectious salmon anaemia virus in Atlantic salmon (Salmo salar L.) cells. 1677 12