Reovirus Infection Enhances Expression of Class I MHC Proteins on Human β-Cell and Rat RINm5F cell

Campbell, Iain L.; Harrison, Leonard C.; Ashcroft, R.G.; Jack, Ian

doi:10.2337/diab.37.3.362

Cited by 30 publications

(9 citation statements)

References 32 publications

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“…Although reoviruses are known to be potent inducers of inlerferon [17.18], recent studies have suggested a direct viral role in the modulation of MHC expression [12,16]. Our data indicate that cytokines released after infection with reoviruses contribute to MHC class I hyperexpression of human TFC.…”

Section: Discussionsupporting

confidence: 54%

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons

Atta

Irving

Powell

et al. 1995

Clinical and Experimental Immunology

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SUMMARYCertain viruses are known to modulate the cellular expression of MHC molecules. We have investigated whether reovirus types I or 3 can alter the normal MHC molecule expression on cultured human thyroid follicular cells (TFC). Primary TFC cultures were established from eight human thyroid donors and MHC class I and II expression was assessed by indirect immunofluorescence microscopy. Both types ot" reovirus enhanced MHC class 1 expression on TFC from all thyroid donors. Class II MHC prolein was strongly induced by type 1 reovirus on TFC from one donor, while weak induction of expression, by either reo-l or reo-3 virus, was noted on the TFC of five other donors. Studies on the mechanism(s) of MHC class I hyperexpression showed that mouse MoAb against the type 3 reovirus haemagglutinin {anti-HA3) reduced the ability ofthe virus to induce hyperexpression of class I MHC molecules on TFC. However, supernatant harvested from type 3 reovirus-infected TFC cultures maintained its ability to enhance class I expression after incubation with anti-HA3. Moreover, adding rabbit anti-sera lo interferon-alpha (IFN-a) or IFN-/? inhibited the increased class 1 MHC expression on TFC by both types of reovirus. These data suggest that reoviruses (types I and 3) can enhance MHC class I on cultured TFC. The mechanism of MHC class I enhancement is most probably through the release of IFN-cv and lFN-/y.

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Section: Discussionsupporting

confidence: 54%

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons

Atta

Irving

Powell

et al. 1995

Clinical and Experimental Immunology

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“…If an alternate mechanism was direct infection of pancreatic islets by RV, plausibility is also supported by our finding that reovirus (from the same Reoviridae family as RV) can infect human islets (37), by reports of pancreatitis associated with RV infection (38,39), and by the fact that a product of the endocrine pancreas, trypsin, renders RV infectious (40). The association of IAA, as well as IA-2 and GADAb, with RV infection could be a consequence of ␤-cell destruction in susceptible individuals, whether secondary to molecular mimicry, direct infection, or direct pancreatic infection followed by mimicry.…”

Section: Discussionsupporting

confidence: 51%

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes.

et al. 2000

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Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children. Diabetes 49:1319-1324, 2000 T ype 1 diabetes is an autoimmune disease that results from the destruction of pancreatic islet ␤-cells in genetically predisposed individuals. A large proportion of the lifetime risk of type 1 diabetes is attributed to environmental agents (1,2), but the only virus shown unequivocally to be responsible for clinical disease is rubella following infection in utero of infants bearing the HLA haplotype B8-(DR3-DQ2) (3). Circulating insulin autoantibodies (IAA), GAD65 antibodies (GADAb), and tyrosine phosphatase IA-2 autoantibodies (IA-2Ab) are markers of islet autoimmunity that predict the T-cell-mediated destruction of ␤-cells (4-6). Peptides in these islet autoantigens that are recognized by T-cells may provide clues to environmental agents that trigger or exacerbate islet autoimmunity through the mechanism of molecular mimicry (7,8).Recently, we identified T-cell epitope peptides in tyrosine phosphatase IA-2 (IA-2) restricted by HLA-DR4 in individuals at risk for type 1 diabetes (9,10). The dominant epitope (amino acid [aa] 805-820) contains a core 9-aa sequence in which 5 aa are identical and 4 aa are homologous with a 9-aa sequence (aa 41-49) within virus protein (VP)7 of rotavirus (RV) serotype G3 and to a lesser extent in the G1 and G2 serotypes. Because the T-cell contact residues in these similar IA-2 and RV VP7 sequences appear to be identical (9), the potential exists for molecular mimicry. Furthermore, just NH 2 -terminal of this region in VP7 is a 12-aa sequence (11) strongly similar to a sequence in GAD65 (aa 117-128) (9) that is a T-cell epitope in HLA-DR4 transgenic mice (12) and DR4-DQ8 homozygous at-risk humans (13). All human RV serotypes in the GenBank database contain the GAD-related sequence. VP7, the major outer capsid protein of RV, is an important determinant of virulence and induces virus-neutralizing antibodies (14). However, elimination of RV infection is predominantly due to T-cells (15). The CD4 T-cell epitopes in VP7 are unknown, but in C57/Bl 6 and BALB/c mice, CD8 T-cell epitopes (15,16) map adjacent to the IA-2-and GAD-like sequences, confirming that this signal sequenc...

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“…By analogy, jun-B might be expressed in stable form in the terminally differentiated (S-cell or upregulated by inflammatory cytokines or both including the IL-6 present in the islet lesion (28,29). Specificity of an anti-jun-B T-cell response would require processing and presentation of islet (p-cell)-specific jun-B epitopes or the persistent effect of a p-cell cytotropic virus (30) or both, or chemotoxin (31) to induce aberrant expression of jun-B. Roep et al (12,13) generated T-cell lines from IDDM subjects to a 38,000-/W r fraction of insulin secretory granules.…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor jun-B is Target of Autoreactive T-Cells in IDDM

Honeyman

Cram²,

Harrison³

1993

Diabetes

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Target antigens defined by autoantibodies in IDDM include insulin, a putative glycolipid that reacts with islet cell antibodies, and a 64,000-/tf r protein recently identified as glutamic acid decarboxylase. In addition, some IDDM sera that contain antibodies to glutamic acid decarboxylase also coprecipitate a 38,000-M r protein from islets. This study used a high titer anti-38,000-M r serum to screen bacteriophage A. cDNA expression libraries and identified human islet and placental clones encoding jun-B, the nuclear transcription protein, of predicted 38,000 M r . Peripheral blood T-cells exhibited significant proliferation in response to a recombinant fragment of jun-B (amino acids 1-180) in 12 of 17 (71%) recent-onset IDDM subjects, 8 of 16 (50%) ICA-positive first-degree relatives of IDDM subjects who were at risk, 3 of 12 (25%) other autoimmune disease subjects, and 0 of 10 healthy control subjects. Proliferation to tetanus toxoid did not differ significantly between the groups. Responses to jun-B were not related to age, sex, or human leukocyte antigen status. Thus, autoreactive T-cells identify a novel antigen, p38 jun-B, in IDDM and appear to indicate subjects at risk for the development of clinical disease. Diabetes 42:626-30,1993

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Reovirus Infection Enhances Expression of Class I MHC Proteins on Human β-Cell and Rat RINm5F cell

Cited by 30 publications

References 32 publications

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes.

Transcription Factor jun-B is Target of Autoreactive T-Cells in IDDM

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