An intracisternal A‐particle sequence codes for an antigen recognized by syngeneic cytolytic T lymphocytes on a mouse spontaneous leukemia

deBergeyck, V.; Plaen, Etienne De; Chomez, Patrick; Boon, Thierry; Pel, Aline Van

doi:10.1002/eji.1830240941

Cited by 37 publications

(12 citation statements)

References 39 publications

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“…In mice, several reports show that murine ERVs encode such antigens. This has been shown for an A-type Gag in spontaneous leukaemia [221], and various Envs in mammary carcinoma [222], melanoma [223], colorectal cancer [224] and in Figure 9. ClustalW alignments of HERV-W and four HERV-H Envs with the mimotopes from [220].…”

Section: T Cell Mediated Immune Responsesmentioning

confidence: 79%

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

2005

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The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. Two types of sequences, HERV-H and HERV-W, have been reported. No known HERV-H or HERV-W copy contains complete ORFs in all prerequisite genes, although several copies have coding potential, and several such sequences are specifically activated in MS, apparently resulting in the production of complete, competent virions. Increased antibody reactivity to specific Gammaretroviral HERV epitopes is found in MS serum and CSF, and cell-mediated immune responses have also been reported. Further, HERV-encoded proteins can have neuropathogenic effects. The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.

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Section: T Cell Mediated Immune Responsesmentioning

confidence: 79%

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

2005

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“…As in mice (de Bergeyck et al 1994), human ERVs associated with tumours may also encode tumour antigens. If a structurally related ERV or non-ERV sequence was expressed in normal tissues, cross-reactivity may be triggered by the tumour.…”

Section: Tumour Immunity and Autoimmunity: Two Faces Of The Erv Puzzlementioning

confidence: 99%

The Potential Roles of Endogenous Retroviruses in Autoimmunity

Nakagawa

Harrison²

1996

Immunological Reviews

115

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Endogenous retroviruses (ERVs) are estimated to comprise up to 1% of human DNA. While the genome of many ERVs is interrupted by termination codons, deletions or frame shift mutations, some ERVs are transcriptionally active and recent studies reveal protein expression or particle formation by human ERVs. ERVs have been implicated as aetiological agents of autoimmune disease, because of their structural and sequence similarities to exogenous retroviruses associated with immune dysregulation and their tissue-specific or differentiation-dependent expression. In fact, retrovirus-like particles distinct from those of known exogenous retroviruses and immune responses to ERV proteins have been observed in autoimmune disease. Quantitatively or structurally aberrant expression of normally cryptic ERVs, induced by environmental or endogenous factors, could initiate autoimmunity through direct or indirect mechanisms. ERVs may lead to immune dysregulation as insertional mutagens or cis-regulatory elements of cellular genes involved in immune function. ERVs may also encode elements like tax in human T-lymphotrophic virus type I (HTLV-I) or tat in human immunodeficiency virus-I (HIV-I) that are capable of transactivating cellular genes. More directly, human ERV gene products themselves may be immunologically active, by analogy with the superantigen activity in the long terminal repeat (LTR) of mouse mammary tumour viruses (MMTV) and the non-specific immunosuppressive activity in mammalian type C retrovirus env protein. Alternatively, increased expression of an ERV protein, or expression of a novel ERV protein not expressed in the thymus during acquisition of immune tolerance, may lead to its perception as a neoantigen. Paraneoplastic syndromes raise the possibility that novel ERV-encoded epitopes expressed by a tumour elicit immunity to cross-reactive epitopes in normal tissues. Recombination events between different but related ERVs, to whose products the host is immunologically tolerant, may also generate new antigenic determinants. Frequently reported humoral immunity to exogenous retrovirus proteins in autoimmune disease could be elicited by cross-reactive ERV proteins. A review of the evidence implicating ERVs in immune dysfunction leads to the conclusion that direct molecular studies are likely to establish a pathogenic role for ERVs in autoimmune disease.

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“…The chimeric mRNA contained an AUG start codon for the Gag protein [34,38] 222-bp upstream of the start codon for IL-2/15Rb ( Figure 3A). Sequence analysis suggested that the chimeric mRNA encoded the Gag-Pol-IL-2/15Rb chimeric protein in which 74 amino acid residues derived from the IAP sequence were fused with the Nterminal of the IL-2Rb.…”

Section: Expression Of Gag-pol-il-2/15rb Chimeric Mrna From the Chimementioning

confidence: 99%

Formation of an active form of the interleukin‐2/15 receptor β‐chain by insertion of the intracisternal A particle in a radiation‐induced mouse thymic lymphoma and its role in tumorigenesis

Ukai

Ishii-Oba²,

Ukai-Tadenuma

et al. 2003

Molecular Carcinogenesis

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Although many reports suggest that aberrant regulation of cytokine signaling pathways via the interleukin-2 receptor (IL-2R) induces tumorigenic transformation, constitutively active IL-2R in tumors has not been reported. We searched for genomic alteration of the IL-2/15R beta-subunit gene (IL-2/15R beta) in cytokine-independent cell lines established from radiation-induced mouse thymic lymphomas. In the TL34 cell line and its primary tumor, one of the IL-2/15R beta alleles was rearranged by the insertion of an intracisternal A particle (IAP) retrotransposon. The IAP-IL2/15R beta chimeric gene expressed chimeric mRNA in which IAP-coding Gag-Pol mRNA was fused to IL-2/15R beta mRNA and coded for Gag-Pol-IL-2/15R beta chimeric protein. Forced expression of the Gag-Pol-IL-2/15R beta chimeric cDNA in a mouse cytotoxic T-cell line (CTLL-2) converted IL-2-dependent cell growth to IL-2-independent growth, suggesting that the chimeric protein activates some of the IL-2 signaling pathways necessary for cell proliferation. Downregulation of the expression of the Gag-Pol-IL-2/15R beta chimeric protein in TL34 by antisense RNA inhibited cell growth, and concomitantly reduced the level of c-myc protein. These results suggest that the Gag-Pol-IL-2/15R beta is a constitutively active form that transmits proliferative signals by expressing downstream target genes, including c-myc. Thus, we demonstrated that the chimeric receptor gene produced by the insertion of an IAP functions as an oncogene by providing IL-2-independent autonomous growth potential.

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An intracisternal A‐particle sequence codes for an antigen recognized by syngeneic cytolytic T lymphocytes on a mouse spontaneous leukemia

Cited by 37 publications

References 39 publications

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

Association of human endogenous retroviruses with multiple sclerosis and possible interactions with herpes viruses

The Potential Roles of Endogenous Retroviruses in Autoimmunity

Formation of an active form of the interleukin‐2/15 receptor β‐chain by insertion of the intracisternal A particle in a radiation‐induced mouse thymic lymphoma and its role in tumorigenesis

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