Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017160 (gastroenteritis)
 11,398 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transmissible gastroenteritis virus, an enteropathogenic coronavirus of swine, is a potent inducer of alpha interferon (IFN-alpha) both in vitro and in vivo. Previous studies have shown that virus-infected fixed cells or viral suspensions were able to induce an early and strong IFN-alpha synthesis by naive lymphocytes. Two monoclonal antibodies directed against the viral membrane glycoprotein M (29,000; formerly E1) were found to markedly inhibit virus-induced IFN production, thus assigning to M protein a potential effector role in this phenomenon (B. Charley and H. Laude, J. Virol. 62:8-11, 1988). The present report describes the selection and characterization of a collection of 125 mutant viruses which escaped complement-mediated neutralization by two IFN induction-blocking anti-M protein monoclonal antibodies. Two of these mutants, designated H92 and dm49-4, were found to exhibit a markedly reduced interferogenic activity. IFN synthesis by lymphocytes incubated with purified suspensions of these mutants was 30- to 300-fold lower than that of the parental virus. The transcription of IFN-alpha genes following induction by each mutant was decreased proportionally, as evidenced by Northern (RNA) blot analysis. The sequence of the M gene of 20 complement-mediated neutralization-resistant mutants, including the 2 defective mutants, was determined by direct sequencing of genome RNA. Thirteen distinct amino acid changes were predicted, all located at positions 6 to 22 from the N terminus of the mature M protein and within the putative ectodomain of the molecule. Two substitutions, Thr-17 to Ile and Ser-19 to Pro, were assumed to generate the defective phenotypes of mutants dm49-4 and H92, respectively. The alteration of an Asn-Ser-Thr sequence in dm49-4 virus led to the synthesis of an M protein devoid of a glycan side chain, which suggests a possible involvement of this structure in IFN induction. Overall, these data supported the view that an interferogenic determinant resides in the N-terminal, exposed part of the molecule and provided further evidence for the direct role of M protein in the induction of IFN-alpha by transmissible gastroenteritis virus. The acronym VIP (viral interferogenic protein) is proposed as a designation for this particular class of proteins.
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PMID:Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. 130 9

Porcine peripheral blood mononuclear cells (PBMC) are induced to produce interferon alpha (IFN alpha) following in vitro exposure to coronavirus TGEV (transmissible gastroenteritis virus)-infected glutaraldehyde-fixed cell monolayers or to TGEV virions. In the present report, we examined the possibility that glycosylation of viral proteins could play a major role in interactions with PBMC leading to the production of IFN alpha. Con A pretreatment of TGEV-infected cell monolayers before fixation with glutaraldehyde and exposure to PBMC caused a dose-dependent inhibition of IFN alpha induction, implying that masking of carbohydrates at the surface of infected cells lowered IFN-alpha-induction. Similarly, inhibition of N-linked glycosylation by tunicamycin during viral infection of cell monolayers altered their ability to induce IFN alpha. In addition, complete cleavage of 'complex type' oligosaccharides by peptide-N-glycohydrolase F lowered the capacity of TGEV virions to induce IFN alpha. Thus, these findings strongly suggest that glycosylation of the viral proteins, and more precisely the presence of complex-type oligosaccharides, is an important requirement for a completely efficient interaction with PBMC leading to the production of IFN-alpha.
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PMID:Glycosylation is required for coronavirus TGEV to induce an efficient production of IFN alpha by blood mononuclear cells. 185 Jan 68

Porcine blood mononuclear cells (PBMC) were shown to produce interferon-alpha (IFN alpha) following incubation with cells infected by a coronavirus, transmissible gastroenteritis virus. Monoclonal antibodies (mAb) with specificities for leukocyte subsets and major histocompatibility complex (MHC) antigens were used to characterize IFN alpha producer cells. The production of IFN alpha was found to be a function of non-phagocytic, non-adherent, non-T, non-B, CD4+ (and to a lesser extent CD8+) MHC-class-II-positive cells. Furthermore, addition of anti-MHC (class II) mAb during PBMC incubation with virus-infected cells reduced IFN yields, suggesting that masking of these surface antigens alters PBMC responsiveness to IFN induction.
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PMID:Characterization of blood mononuclear cells producing IFN alpha following induction by coronavirus-infected cells (porcine transmissible gastroenteritis virus). 216 6

Epithelial cells infected with the coronavirus transmissible gastroenteritis virus (TGEV) and fixed by glutaraldehyde induced a high alpha interferon (IFN-alpha) production in nonimmune porcine as well as human or bovine peripheral blood mononuclear cells (PBMC). IFN-alpha was detected as early as 3 h after exposure of PBMC to infected cells and at producer/inducer cell ratios as low as 1/1. Two of four monoclonal antibodies directed against the viral transmembrane glycoprotein E1 could block the IFN-inducing capacity of both TGEV-infected cells and viral particles. On the other hand, IFN-alpha induction was not markedly affected by monoclonal antibodies directed against other E1 epitopes, against peplomer glycoprotein E2, or against nucleocapsid protein. Thus, these findings strongly imply that IFN induction by TGEV results from interactions between an outer membrane domain of E1 and the PBMC membrane.
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PMID:Induction of alpha interferon by transmissible gastroenteritis coronavirus: role of transmembrane glycoprotein E1. 282 58

Recombinant porcine interferon gamma (rPoIFN gamma) induced a dose-dependent inhibition of the cytopathic effect produced by vesicular stomatitis virus (VSV) challenge of both homologous and heterologous (bovine) cell lines. In addition, an antiviral effect of rPoIFN gamma was demonstrable against the coronavirus transmissible gastroenteritis virus (TGEV) infection of porcine epithelial cells and of pulmonary macrophages. A rabbit anti-PoIFN gamma antiserum was prepared and shown to specifically neutralize the antiviral effects of natural and recombinant porcine IFN gamma preparations. This antiserum could also neutralize recombinant bovine IFN gamma but not recombinant human IFN gamma. These results suggest antigenic homology of porcine and bovine IFN gamma but antigenic differences between these molecules and human IFN gamma.
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PMID:Antiviral and antigenic properties of recombinant porcine interferon gamma. 284 5

The effects of irradiation were studied on porcine interferon-alpha (IFN-alpha) secreting cells (IFN-alpha SC). IFN-alpha SC were characterized by an ELISPOT assay on non-adherent PBMC following incubation with the transmissible gastroenteritis coronavirus. In vitro irradiation of PBMC was followed by a decrease in the number of IFN-alpha SC while IFN-gamma production and cell viability were not affected. These data indicate that porcine IFN-alpha SC are relatively radiosensitive. Indeed, the frequency of blood IFN-alpha SC decreased markedly and rapidly after in vivo whole body or partial lymphoid irradiation. In addition, within several days of compatible bone-marrow engraftment in the irradiated animals, the number of blood IFN-alpha SC returned to normal values. These data demonstrate that circulating porcine IFN-alpha SC are derived from bone-marrow progenitors.
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PMID:Frequency of interferon-alpha-secreting blood leukocytes in irradiated and bone-marrow-grafted pigs. 755 Apr

Interferon-gamma (IFN-gamma) and a type I IFN (spI IFN) are transiently coexpressed by trophoblastic cells of pig conceptuses at implantation between day 12 and day 20 of gestation. The local effects of these trophoblastic IFNs were examined on endometrial cells and on trophoblast by measuring antiviral activity and the induction of (2',5')-oligoadenylate synthetase activity. Trophoblastic vesicles were shown to be susceptible to infection by vesicular stomatitis virus and transmissible gastroenteritis virus. Vesicular stomatitis virus multiplied by about 1000 times in trophoblastic vesicles, and endogenous trophoblastic IFNs or exogenous recombinant IFN-gamma or spI IFN had no effect on virus production. No (2',5')-oligoadenylate synthetase activity could be measured on the trophoblast, even after treatment with IFN-gamma or spI IFN. These results clearly show that trophoblastic IFNs cannot induce antiviral resistance or (2',5')-oligoadenylate synthetase activity in the trophoblast, suggesting that these IFNs have no autocrine function. Endometrial epithelial and stromal cells in primary cultures displayed distinct sensitivity to the antiviral effect of IFN-gamma and spI IFN. Stromal fibroblasts were highly sensitive to spI IFN but weakly sensitive to IFN-gamma; epithelial cells were sensitive to both IFNs. The same sensitivity pattern was obtained when measuring the (2',5')-oligoadenylate synthetase activity. Flushing fluid, containing IFN-gamma and type I IFN, was a potent inducer of antiviral effect and (2',5')-oligoadenylate synthetase activity. It is therefore postulated that the endometrial epithelium is the most likely target of trophoblastic IFNs. It is possible that these IFNs play a role in the viral protection of conceptuses.
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PMID:Paracrine activities of porcine trophoblastic interferons. 779 12

Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIPV) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease. Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems. Coronaviruses are spherical, enveloped viruses, ranging from 80-160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150-200 kDa), the integral membrane glycoprotein (M; 20-30 kDa) and the nucleocapsid phosphoprotein (N; 43-50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60-65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA. Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of alpha IFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Coronavirus immunogens. 811 87

We studied the expression of interferon alpha (IFN alpha)-mRNA in porcine non-adherent peripheral blood mononuclear cells (PBMC) after induction by the coronavirus transmissible gastroenteritis virus (TGEV). We found that protein synthesis inhibition by cycloheximide (CHX) blocked IFN alpha-mRNA expression, except when PBMC were preincubated with a conditioned medium as a potential source of cytokines. These data indicate that IFN alpha-mRNA induction by TGEV requires de novo synthesis of proteins. Moreover, they suggest that IFN alpha-mRNA induction in porcine leukocytes by TGEV involves mechanisms identical to those described for the herpes simplex virus in humans. In addition, experiments performed with a TGEV mutant, dm 49-4, previously characterized for its low ability to induce IFN alpha, showed that addition of a conditioned medium could not normalize its IFN alpha-inducing ability. Therefore, the defect of the dm49-4 mutant may be at the level of the final triggering signal to PBMC.
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PMID:Coronavirus transmissible gastroenteritis virus-mediated induction of IFN alpha-mRNA in porcine leukocytes requires prior synthesis of soluble proteins. 814 54

Porcine blood mononuclear cells (PBMC) were shown to secrete interferon alpha (IFN-alpha) after induction by a coronavirus, the transmissible gastroenteritis virus (TGEV). IFN-alpha producing cells, referred to as natural interferon alpha producing (NIP) cells, were detected by an ELISPOT assay using anti-porcine IFN-alpha monoclonal antibodies. The frequency of NIP cells among blood cells is low, at most 40-110 per 10(5) PBMC and each NIP cell was found to produce several units of IFN. We have shown that NIP cell frequency and IFN yield per cell gradually increased with the age of the donor animals, from the neonatal period to the adult age, with a significant increase around puberty. Our present results also indicate that NIP cells may be influenced by physiological and genetic factors; thus (1) NIP cell frequency and IFN yield per cell were decreased during lactation; (2) Chinese (Meishan) pigs were found to have higher NIP cell frequency and IFN yield per cell than European (Large White) animals.
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PMID:Age-related increase of porcine natural interferon alpha producing cell frequency and of interferon yield per cell. 823 91


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