Cross-talk of the environment with the host genome and the immune system through endogenous retroviruses in systemic lupus erythematosus

Lupus ◽  
2009 ◽  
Vol 18 (13) ◽  
pp. 1136-1143 ◽  
Author(s):  
M. Blank ◽  
Y. Shoenfeld ◽  
A. Perl
Keyword(s):  
Lupus Erythematosus ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Stress Hormones ◽  
Cross Reactivity ◽  
Histone Deacetylation ◽  
Endogenous Retroviruses ◽  
Autoimmune Response ◽  
Human Endogenous Retroviruses ◽  
Ultraviolet Exposure

Environmental factors are capable of triggering the expression of human endogenous retroviruses and induce an autoimmune response. Infection can promote the expression of human endogenous retroviruses by molecular mimicry or by functional mimicry. There are additional mechanisms which may control the expression of human endogenous retroviruses, such as epigenetic status of the genome (hypomethylation, histone deacetylation). Ultraviolet exposure, chemicals/drugs, injury/stress, hormones, all as a single cause or in a concert, may modulate the involvement of human endogenous retroviruses in pathogenic processes. In the current review we summarize the current knowledge on infections, molecular mimicry, cross-reactivity and epigenetics contribution for trigger human endogenous retroviruses expression and pathogenesis in lupus patients. Lupus (2009) 18, 1136—1143.

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

2013 ◽  
Vol 7 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Nicola Tugnet ◽  
Paul Rylance ◽  
Denise Roden ◽  
Malgorzata Trela ◽  
Paul Nelson
Keyword(s):  
Rheumatic Disease ◽  
Rheumatic Diseases ◽  
Chronic Conditions ◽  
Molecular Mimicry ◽  
Endogenous Retroviruses ◽  
Clinical Implications ◽  
Human Endogenous Retroviruses ◽  
Novel Treatments ◽  
Autoimmune Rheumatic Diseases ◽  
Autoimmune Rheumatic Disease

Autoimmune rheumatic diseases, such as RA and SLE, are caused by genetic, hormonal and environmental factors. Human Endogenous Retroviruses (HERVs) may be triggers of autoimmune rheumatic disease. HERVs are fossil viruses that began to be integrated into the human genome some 30-40 million years ago and now make up 8% of the genome. Evidence suggests HERVs may cause RA and SLE, among other rheumatic diseases. The key mechanisms by which HERVS are postulated to cause disease include molecular mimicry and immune dysregulation. Identification of HERVs in RA and SLE could lead to novel treatments for these chronic conditions. This review summarises the evidence for HERVs as contributors to autoimmune rheumatic disease and the clinical implications and mechanisms of pathogenesis are discussed.

scholarly journals HSV-1 and Endogenous Retroviruses as Risk Factors in Demyelination

2021 ◽  
Vol 22 (11) ◽  
pp. 5738
Author(s):  
Raquel Bello-Morales ◽  
Sabina Andreu ◽  
Inés Ripa ◽  
José Antonio López-Guerrero
Keyword(s):  
Risk Factor ◽  
Dna Sequences ◽  
Demyelinating Disease ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Endogenous Retroviruses ◽  
Unknown Etiology ◽  
Genetic And Environmental Factors ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that can infect the peripheral and central nervous systems, and it has been implicated in demyelinating and neurodegenerative processes. Transposable elements (TEs) are DNA sequences that can move from one genomic location to another. TEs have been linked to several diseases affecting the central nervous system (CNS), including multiple sclerosis (MS), a demyelinating disease of unknown etiology influenced by genetic and environmental factors. Exogenous viral transactivators may activate certain retrotransposons or class I TEs. In this context, several herpesviruses have been linked to MS, and one of them, HSV-1, might act as a risk factor by mediating processes such as molecular mimicry, remyelination, and activity of endogenous retroviruses (ERVs). Several herpesviruses have been involved in the regulation of human ERVs (HERVs), and HSV-1 in particular can modulate HERVs in cells involved in MS pathogenesis. This review exposes current knowledge about the relationship between HSV-1 and human ERVs, focusing on their contribution as a risk factor for MS.

Systemic lupus erythematosus and human endogenous retroviruses

2003 ◽  
Vol 13 (2) ◽  
pp. 107-113 ◽  
Author(s):  
Iwao Sekigawa ◽  
Hitoshi Ogasawara ◽  
Toshio Naito ◽  
Hiroshi Kaneko ◽  
Takashi Hishikawa ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Endogenous Retroviruses ◽  
Systemic Lupus ◽  
Human Endogenous Retroviruses

scholarly journals Transcriptomic analysis of human endogenous retroviruses in systemic lupus erythematosus

2019 ◽  
Vol 116 (43) ◽  
pp. 21350-21351 ◽  
Author(s):  
Luis P. Iñiguez ◽  
Miguel de Mulder Rougvie ◽  
Nathaniel Stearrett ◽  
Richard B. Jones ◽  
Christopher E. Ormsby ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Transcriptomic Analysis ◽  
Endogenous Retroviruses ◽  
Systemic Lupus ◽  
Human Endogenous Retroviruses

Antibody specificity and promiscuity

2019 ◽  
Vol 476 (3) ◽  
pp. 433-447 ◽  
Author(s):  
Deepti Jain ◽  
Dinakar M. Salunke
Keyword(s):  
Immune System ◽  
Molecular Mimicry ◽  
A Priori ◽  
Rapid Evolution ◽  
Cross Reactivity ◽  
Immune Defense ◽  
Autoimmune Response ◽  
Antigenic Determinants ◽  
Antibody Specificity ◽  
Foreign Antigen

Abstract The immune system is capable of making antibodies against anything that is foreign, yet it does not react against components of self. In that sense, a fundamental requirement of the body's immune defense is specificity. Remarkably, this ability to specifically attack foreign antigens is directed even against antigens that have not been encountered a priori by the immune system. The specificity of an antibody for the foreign antigen evolves through an iterative process of somatic mutations followed by selection. There is, however, accumulating evidence that the antibodies are often functionally promiscuous or multi-specific which can lead to their binding to more than one antigen. An important cause of antibody cross-reactivity is molecular mimicry. Molecular mimicry has been implicated in the generation of autoimmune response. When foreign antigen shares similarity with the component of self, the antibodies generated could result in an autoimmune response. The focus of this review is to capture the contrast between specificity and promiscuity and the structural mechanisms employed by the antibodies to accomplish promiscuity, at the molecular level. The conundrum between the specificity of the immune system for foreign antigens on the one hand and the multi-reactivity of the antibody on the other has been addressed. Antibody specificity in the context of the rapid evolution of the antigenic determinants and molecular mimicry displayed by antigens are also discussed.

scholarly journals Expression of Human Endogenous Retroviruses in Systemic Lupus Erythematosus: Multiomic Integration With Gene Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Nathaniel Stearrett ◽  
Tyson Dawson ◽  
Ali Rahnavard ◽  
Prathyusha Bachali ◽  
Matthew L. Bendall ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Differentially Expressed Genes ◽  
Lupus Erythematosus ◽  
Nuclear Material ◽  
Endogenous Retroviruses ◽  
Differentially Expressed ◽  
Potential Contribution ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Human Endogenous Retroviruses

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies predominantly to nuclear material. Many aspects of disease pathology are mediated by the deposition of nucleic acid containing immune complexes, which also induce the type 1interferon response, a characteristic feature of SLE. Notably, SLE is remarkably heterogeneous, with a variety of organs involved in different individuals, who also show variation in disease severity related to their ancestries. Here, we probed one potential contribution to disease heterogeneity as well as a possible source of immunoreactive nucleic acids by exploring the expression of human endogenous retroviruses (HERVs). We investigated the expression of HERVs in SLE and their potential relationship to SLE features and the expression of biochemical pathways, including the interferon gene signature (IGS). Towards this goal, we analyzed available and new RNA-Seq data from two independent whole blood studies using Telescope. We identified 481 locus specific HERV encoding regions that are differentially expressed between case and control individuals with only 14% overlap of differentially expressed HERVs between these two datasets. We identified significant differences between differentially expressed HERVs and non-differentially expressed HERVs between the two datasets. We also characterized the host differentially expressed genes and tested their association with the differentially expressed HERVs. We found that differentially expressed HERVs were significantly more physically proximal to host differentially expressed genes than non-differentially expressed HERVs. Finally, we capitalized on locus specific resolution of HERV mapping to identify key molecular pathways impacted by differential HERV expression in people with SLE.

scholarly journals Human endogenous retroviruses: nature, occurrence, and clinical implications in human disease.

1996 ◽  
Vol 9 (1) ◽  
pp. 72-99 ◽  
Author(s):  
H B Urnovitz ◽  
W H Murphy
Keyword(s):  
Lupus Erythematosus ◽  
Human Disease ◽  
Leukemia Virus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
T Cell Leukemia Virus ◽  
Health And Disease ◽  
Disease Entities

Retroviral diagnostics have become standard in human laboratory medicine. While current emphasis is placed on the human exogenous viruses (human immunodeficiency virus and human T-cell leukemia virus), evidence implicating human endogenous retroviruses (HERVs) in various human disease entities continues to mount. Literature on the occurrence of HERVs in human tissues and cells was analyzed. Substantial evidence documents that retrovirus particles were clearly demonstrable in various tissues and cells in both health and disease and were abundant in the placenta and that their occurrence could be implicated in some of the reproductive diseases. The characteristics of HERVs are summarized, mechanisms of replication and regulation are outlined, and the consistent hormonal responsiveness of HERVs is noted. Clear evidence implicating HERV gene products as participants in glomerulonephritis in some cases of systemic lupus erythematosus is adduced. Data implicating HERVs as etiologic factors in reproductive diseases, in some of the autoimmune diseases, in some forms of rheumatoid arthritis and connective tissue disease, in psoriasis, and in some of the inflammatory neurologic diseases are reviewed. The current major needs are to improve methods for HERV detection, to identify the most appropriate HERV prototypes, and to develop diagnostic reagents so that the putative biologic and pathologic roles of HERVs can be better evaluated.

scholarly journals The Role of Herpes Simplex Virus Type 1 Infection in Demyelination of the Central Nervous System

2020 ◽  
Vol 21 (14) ◽  
pp. 5026 ◽  
Author(s):  
Raquel Bello-Morales ◽  
Sabina Andreu ◽  
José Antonio López-Guerrero
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Herpes Simplex ◽  
Molecular Mimicry ◽  
Current Knowledge ◽  
Endogenous Retroviruses ◽  
Surrounding Tissue ◽  
The Central Nervous System ◽  
Hsv 1

Herpes simplex type 1 (HSV-1) is a neurotropic virus that infects the peripheral and central nervous systems. After primary infection in epithelial cells, HSV-1 spreads retrogradely to the peripheral nervous system (PNS), where it establishes a latent infection in the trigeminal ganglia (TG). The virus can reactivate from the latent state, traveling anterogradely along the axon and replicating in the local surrounding tissue. Occasionally, HSV-1 may spread trans-synaptically from the TG to the brainstem, from where it may disseminate to higher areas of the central nervous system (CNS). It is not completely understood how HSV-1 reaches the CNS, although the most accepted idea is retrograde transport through the trigeminal or olfactory tracts. Once in the CNS, HSV-1 may induce demyelination, either as a direct trigger or as a risk factor, modulating processes such as remyelination, regulation of endogenous retroviruses, or molecular mimicry. In this review, we describe the current knowledge about the involvement of HSV-1 in demyelination, describing the pathways used by this herpesvirus to spread throughout the CNS and discussing the data that suggest its implication in demyelinating processes.

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