Human Endogenous Retroviruses (HERVs) and Autoimmune Rheumatic Disease: Is There a Link?

Tugnet, Nicola; Rylance, Paul; Roden, Denise A.; Trela, Malgorzata; Nelson, Paul N.

doi:10.2174/1874312901307010013

Cited by 81 publications

(71 citation statements)

References 86 publications

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“…An association of human autoimmune diseases with ERVs has also been postulated (22). Such diseases may be hypothesized to result from dysregulation of adaptive rather than strictly innate immune activation in that retroviruses, MAVS, cGAS, and STING serve as components of the normal TI-2 B cell signaling apparatus.…”

Section: Discussionmentioning

confidence: 99%

MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses

Zeng

Shi

et al. 2014

Science

100

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Multivalent molecules with repetitive structures including bacterial capsular polysaccharides and viral capsids elicit antibody responses through B cell receptor (BCR) crosslinking in the absence of T cell help. We report that immunization with these T cell-independent type 2 (TI-2) antigens causes upregulation of endogenous retrovirus (ERV) RNAs in antigen-specific mouse B cells. These RNAs are detected via a MAVS-dependent RNA sensing pathway or reverse transcribed and detected via the cGAS-cGAMP-STING pathway, triggering a second, sustained wave of signaling that promotes specific IgM production. Deficiency of both MAVS and cGAS, or treatment of MAVS-deficient mice with reverse transcriptase inhibitors, dramatically inhibits TI-2 antibody responses. These findings suggest that ERV and two innate sensing pathways that detect them are integral components of the TI-2 B cell signaling apparatus.

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Section: Discussionmentioning

confidence: 99%

MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses

Zeng

Shi

et al. 2014

Science

100

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“…The biased expression of proviral proteins in human tissues may trigger autoimmune diseases [151,152]. This was indicated first by increased proviral transcript levels [153] and finding anti-HERV protein antibodies in sera from several groups of patients suffering from these systemic disorders [37].…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

Molecular functions of human endogenous retroviruses in health and disease

Suntsova

Garazha

Ivanova

et al. 2015

Cell. Mol. Life Sci.

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Human endogenous retroviruses (HERVs) and related genetic elements form 504 distinct families and occupy ~8% of human genome. Recent success of high-throughput experimental technologies facilitated understanding functional impact of HERVs for molecular machinery of human cells. HERVs encode active retroviral proteins, which may exert important physiological functions in the body, but also may be involved in the progression of cancer and numerous human autoimmune, neurological and infectious diseases. The spectrum of related malignancies includes, but not limits to, multiple sclerosis, psoriasis, lupus, schizophrenia, multiple cancer types and HIV. In addition, HERVs regulate expression of the neighboring host genes and modify genomic regulatory landscape, e.g., by providing regulatory modules like transcription factor binding sites (TFBS). Indeed, recent bioinformatic profiling identified ~110,000 regulatory active HERV elements, which formed at least ~320,000 human TFBS. These and other peculiarities of HERVs might have played an important role in human evolution and speciation. In this paper, we focus on the current progress in understanding of normal and pathological molecular niches of HERVs, on their implications in human evolution, normal physiology and disease. We also review the available databases dealing with various aspects of HERV genetics.

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“…Different regulation of HERV expression has been associated with many inflammatory diseases like systemic lupus erythematosis, rheumatoid arthritis and so on [47-51]. However, it is questionable if HERVs are only harmless bystanders or core elements of the respective diseases.…”

Section: Discussionmentioning

confidence: 99%

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

et al. 2018

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Background: Eight percent of the human genome consists of human endogenous retroviruses (HERV). These genetic elements are remnants of ancient retroviral germ-line infections. Altered HERV expression is associated with several chronic inflammatory diseases. A physiological role of the HERV-derived proteins syncytin-1 and -2 has been described for the integrity of the human placental cell layer in terms of maintaining feto-maternal tolerance. The aim of this project was to investigate HERV expression in Crohn’s disease (CD) with a further focus on syncytins in the gut. Material and Methods: Seventy-four ileal and colonic tissue samples of CD patients and healthy controls have been investigated for mRNA expression of major HERV groups by a comprehensive microarray screening. The most prominent differences have been validated by qRT-PCR. Immunohistochemistry (IHC), Western Blot (WB) and qRT-PCR were performed for syncytin-1 and -2. Results: HERV microarray screening revealed a distinct expression profile in ileal and colonic tissue, as well as differential expression in CD compared to healthy controls. qRT-PCR validated differential expression of at least 3 HERV-groups in CD. qRT-PCR, IHC and WB showed a tissue-dependent diminished epithelial expression of syncytins in inflamed CD. Conclusion: For the first time, HERV expression has been comprehensively studied in the gut. Between CD and healthy controls we could show a tissue dependent differential HERV expression profile. Notably, we could show that syncytin-1 and -2 are expressed in the epithelial layer in ileal and colonic tissue samples, whereas their diminished tissue-dependent expression in inflamed CD might modulate inflammatory processes at the gut barrier.

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Human Endogenous Retroviruses (HERVs) and Autoimmune Rheumatic Disease: Is There a Link?

Cited by 81 publications

References 86 publications

MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses

MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses

Molecular functions of human endogenous retroviruses in health and disease

Human Endogenous Retroviruses: Residues of Ancient Times Are Differentially Expressed in Crohn’s Disease

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