Autoantibodies to human endogenous retrovirus-K are frequently detected in health and disease and react with multiple epitopes

Hervé, Christine; Lugli, Elena B.; Brand, Alexander; Griffiths, David J.; Venables, P. J. W.

doi:10.1046/j.1365-2249.2002.01735.x

Cited by 57 publications

(61 citation statements)

References 38 publications

(57 reference statements)

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“…Herve et al (17) characterized retroviral antigens in the context of autoimmune diseases. A variant HERV-K provirus described Box plots comparing the reactivity of sera (given as absorbance) from melanoma patients and patients with autoimmune disorders.…”

Section: Resultsmentioning

confidence: 99%

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Identification of a Melanoma Marker Derived from Melanoma-Associated Endogenous Retroviruses

Humer

Waltenberger²,

Grassauer³

et al. 2006

Cancer Research

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We previously described the expression of melanomaassociated endogenous retrovirus (MERV) proteins and viral particles in human melanomas and metastases. The objective of the present study was to determine whether a humoral immune response to MERV proteins occurs in melanoma. Candidate B-cell epitopes on MERV proteins were predicted using bioinformatic screening. The reactivity of MERV peptides corresponding to the predicted epitopes with antibodies prevalent in sera of melanoma patients was analyzed. An immunodominant peptide located in the env protein of MERV was identified. Subsequent analyzes using 81 samples from stage I to stage IV melanoma patients and 95 sera from healthy subjects revealed statistically significant differences in seroprevalence of antibodies in melanoma sera samples when compared with reference samples from healthy subjects. The prevalence of anti-MERV antibodies in melanoma patient sera was confirmed by immunofluorescence on env-transfected cells. These data indicate the potential of this candidate peptide as target for diagnosis and immunotherapy.

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Section: Resultsmentioning

confidence: 99%

“…Overexpression of HERV-K10-like gag genes in the blood cells of leukemia patients was shown using real-time reverse transcription-PCR (16). In addition, autoantibodies to HERV-K in autoimmune diseases were described (17).…”

Section: Introductionmentioning

confidence: 99%

Identification of a Melanoma Marker Derived from Melanoma-Associated Endogenous Retroviruses

Humer

Waltenberger²,

Grassauer³

et al. 2006

Cancer Research

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“…It therefore remains controversial whether many of these reactivities were indeed induced by endogenous retroviral antigens or whether they represent cross-reactions elicited by exogenous retroviruses or by nonviral antigens such as the cellular ribonucleoproteins, known to resemble some regions of Gag (51). However, in a recent study, antibodies recognizing multiple Env epitopes of two HERV-K proviruses were found in Ϸ30% of healthy individuals (52). Very solid data are also available documenting a significant increase in frequency and titer of antibodies directed against HERV-K proteins in patients suffering from testicular tumors.…”

Section: Production Of Herv Particlesmentioning

confidence: 99%

“…There is also circumstantial evidence that HERV expression is elevated by proinflammatory cytokines (55,56). A number of studies have, indeed, shown that HERV-encoded proteins are expressed in inflamed tissues, and antibodies to HERVs in patients with autoimmune diseases such as systemic lupus erythematodes (SLE), Sjogren's syndrome, multiple sclerosis, and related dis- eases were frequently detected (46,52,(57)(58)(59)(60). These studies are often cited to support a role for HERVs in the etiology or progression of these disorders.…”

Section: Production Of Herv Particlesmentioning

confidence: 99%

Retroelements and the human genome: New perspectives on an old relation

Bannert

Kurth

2004

Proc. Natl. Acad. Sci. U.S.A.

459

418

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Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.A lmost half of the mammalian genome is derived from ancient transposable elements. The two general types, (DNA)-transposons and retroelements, often regarded as ''selfish DNA parasites or junk DNA,'' encompass Ϸ2.8% and 42.2% of the human genome, respectively (1, 2). This striking finding is one of the many insights from recent large-scale sequencing projects that have provided the most valuable information in this field since the initial discovery of mobile elements in 1956 by Barbara McClintock (3, 4). Whereas DNA-transposons amplify without an RNA intermediate, retroelements rely on an RNA transcript that is retrotranscribed by a reverse transcriptase before integration in the genome. Here, we briefly review the characteristics of retroelements, their present classification, and the available evidence for their biological significance and function in normal and pathological processes. The focus is on human endogenous retroviruses (HERVs), the remnants of ancient germ-cell infections. Although most of the HERV proviruses have undergone extensive deletions and mutations, some have retained ORFs coding for functional proteins. A few families, including the HERV-K (HML-2) group, have been shown to form viral particles (5, 6), and an apparently intact provirus has recently been discovered in a small fraction of the human population, indicating a very recent acquisition (5-7). Classification of RetroelementsRetroelements constitute 90% of the Ϸ3 million transposable elements present in the human genome (1). They are split into two large groups, the non-LTR and LTR elements (Fig. 1). Two of the non-LTR members are present in extremely high copy numbers in the mammalian germ line: the short interspersed elements (SINE) with the prominent Alu and MIR repeats and the long-terminal interspersed elements (LINE) containing the...

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“…Epitope mapping using pepscan provides a useful adjunct to the characterisation of MAbs [4] and has been used in identifying epitopes on macromolecules including allergens and components of viruses [20,21]. However, an important caveat of pepscan is that the technique is biased towards antibodies recognising linear, as opposed to conformational epitopes.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of epitopes of pan-IgG/anti-G3m(u) and anti-Fc monoclonal antibodies

et al. 2003

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The characterisation of monoclonal antibodies (MAbs) and their epitopes is important prior to their application as molecular probes. In this study, Western blotting using IgG1 Fc and pFc? fragments was employed to screen seven MAbs before pepscan analysis to determine their reactivity to potentially linear epitopes. MAbs PNF69C, PNF110A, X1A11 and MAbs WC2, G7C, JD312, 1A1 detected epitopes within the C H 3 and C H 2 domains, respectively. However, only four MAbs showed pepscan profiles that highlighted likely target residues. In particular, MAbs PNF69C and PNF110A that have previously been characterised with pan-IgG and anti-G3m(u) specificity, detected the peptide motif 338-KAKGQPR-344 which was located within the N-terminal region of the C H 3 domain. Furthermore the majority of residues were present in all four IgG subclasses. Consequently the peptide identified was consistent with the pan-IgG nature of these antibodies. By using PCImdad, a molecular display programme, this sequence was visualised as surface accessible, located in the C H 2/C H 3 inter-domain region and proximal to the residue arginine 435 . It is speculated that this residue may be important for phenotypic expression of G3m(u) and specificity of these reagents. Pepscan analysis of MAbs G7C and JD312 (both pan-IgG) highlighted the core peptide sequence 290-KPREE-294, which was present in the C H 2 domain and was common to all four IgG subclasses. PCImdad also showed this region to be highly accessible and was consistent with previous bioinformatic and autoimmune analysis of IgG. Overall these MAbs may serve as useful anti-IgG or antiG3m(u) reagents and probes of immunoglobulin structure. #

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Autoantibodies to human endogenous retrovirus-K are frequently detected in health and disease and react with multiple epitopes

Cited by 57 publications

References 38 publications

Identification of a Melanoma Marker Derived from Melanoma-Associated Endogenous Retroviruses

Identification of a Melanoma Marker Derived from Melanoma-Associated Endogenous Retroviruses

Retroelements and the human genome: New perspectives on an old relation

Characterisation of epitopes of pan-IgG/anti-G3m(u) and anti-Fc monoclonal antibodies

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