Endogenous retroviral pathogenesis in lupus

Perl, Andras; Fernandez, David; Telarico, Tiffany; Phillips, Paul E

doi:10.1097/bor.0b013e32833c6297

Cited by 75Systemic Lupus Erythematosus ResearchSystemic Sclerosis and Related DiseasesImmune Response and Inflammation

Endogenous retroviral pathogenesis in lupus

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Perl, Andras, Fernandez, David, Telarico, Tiffany, Phillips, Paul E·2010·Current Opinion in Rheumatology

DOI 10.1097/bor.0b013e32833c6297PMC PMC5314925

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Abstract

PURPOSE OF REVIEW: Genetic and environmental factors influence the development of systemic lupus erythematosus (SLE). Endogenous retroviruses (ERVs) are proposed as a molecular link between the human genome and environmental factors, such as viruses, in lupus pathogenesis. RECENT FINDINGS: The HRES-1 human ERV encodes a 28-kD nuclear autoantigen and a 24-kD small GTP-ase, termed HRES-1/Rab4. HRES-1/p28 is a target of cross-reactive antiviral antibodies, whereas HRES-1/Rab4 regulates the surface expression of CD4 via endosome recycling. The tat gene of HIV-1 induces the expression of HRES-1/Rab4, which in turn downregulates expression of CD4 and susceptibility to reinfection by HIV-1. HRES-1/Rab4 is overexpressed in lupus T cells where it correlates with increased recycling of CD4 and CD3 and contributes to downregulation of CD3/TCRzeta via lysosomal degradation. Chilblain lupus has been linked to the deficiency of 3'-5' repair exonuclease Trex1 that metabolizes DNA reverse-transcribed from ERV. Trex1 deficiency or blocked integration of ERV-encoded DNA also promotes lupus in murine models. SUMMARY: ERV proteins may trigger lupus through structural and functional molecular mimicry, whereas the accumulation of ERV-derived nucleic acids stimulates interferon and anti-DNA antibody production in SLE.

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Endogenous retroviral antigens do not cause complete immunological tolerance and both T and B cell responses are frequently detected in both mice and humans.
“It is also clear, however, that endogenous retroviral antigens do not cause complete immunological tolerance and both T and B cell responses are frequently detected in both mice and humans 33,34,36–41.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [39]
The Introduction (page not supplied) reports endogenous retroviral gp70 in immune-complex deposits of lupus-prone mice and autoantigenicity of endogenous retroviral sequences in patients with lupus. The Molecular mimicry section reports antibodies to an endogenous retroviral antigen in human lupus sera. These passages support incomplete tolerance in those settings, but do not establish that both T- and B-cell responses to such antigens are frequently detected in both mice and humans. (LLM, conf=0.82)
Experimental — accuracy not yet measured
HERV-encoded antigens have been implicated as putative autoantigens in the development of human autoimmune diseases.
“HERV-encoded antigens have also been implicated as putative autoantigens in the development of human autoimmune diseases 36–39,43,44.”
From Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis (2013) · cites this paper as [39]

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The p85α Subunit of Phosphatidylinositol 3′-Kinase Binds to and Stimulates the GTPase Activity of Rab Proteins
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The curiously suspicious: a role for Epstein-Barr virus in lupus
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Human endogenous retroviruslike genome with type C pol sequences and gag sequences related to human T-cell lymphotropic viruses
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Identification and characterization of novel human endogenous retroviral sequences prefentially expressed in undifferentiated embryonal carcinoma cells
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Transcriptional Activation of Endogenous Retroviral Sequences in Human Epidermal Keratinocytes by UVB Irradiation
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Red cell autoantibodies in patients with acquired immune deficiency syndrome
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The Stress Hormone Corticosterone Increases Synaptic α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors via Serum- and Glucocorticoid-inducible Kinase (SGK) Regulation of the GDI-Rab4 Complex
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Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR zeta-chain.
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Detection of TT Virus in Lymph Node Biopsies of B-Cell Lymphoma and Hodgkin's Disease, and its Association with EBV Infection
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Regulation of CD4 Expression via Recycling by HRES-1/RAB4 Controls Susceptibility to HIV Infection*
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Mechanisms of viral pathogenesis in rheumatic disease
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The expression of human endogenous retrovirus-3 in fetal cardiac tissue and antibodies in congenital heart block.
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HERV-F(XA34) is a full-length human endogenous retrovirus expressed in placental and fetal tissues
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Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus
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Overexpression and mutations of p53 in metastatic malignant melanomas
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Lupus Susceptibility Genes on Human Chromosome 1
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TCR Activation Eliminates Glutamate Receptor GluR3 from the Cell Surface of Normal Human T Cells, via an Autocrine/Paracrine Granzyme B-Mediated Proteolytic Cleavage
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Cytokine Regulation of env Gene Expression of Human Endogenous Retrovirus-R in Human Vascular Endothelial Cells
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Polymorphic genotypes of the HRES-1 human endogenous retrovirus locus correlate with systemic lupus erythematosus and autoreactivity
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A variable number of tandem repeats locus within the human complement C2 gene is associated with a retroposon derived from a human endogenous retrovirus.
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Selective antibody reactivity with peptides from human endogenous retroviruses and nonviral poly(amino acids) in patients with systemic lupus erythematosus
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Autoimmune epilepsy: Distinct subpopulations of epilepsy patients harbor serum autoantibodies to either glutamate/AMPA receptor GluR3, glutamate/NMDA receptor subunit NR2A or double-stranded DNA
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Vpu-Mediated Degradation of CD4 Reconstituted in Yeast Reveals Mechanistic Differences to Cellular ER-Associated Protein Degradation
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Human endogenous retrovirus K10 encodes a functional integrase
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Role of endogenous retroviruses in autoimmune diseases
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Tyrosine and serine protein kinase activities associated with ligand-induced internalized TCR/CD3 complexes
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HIV-1-Related Thrombocytopenia
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Analysis of thymic endogenous retroviral expression in murine lupus. Genetic and immune studies.
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Heterogeneous Expression and Coordinate Regulation of Endogenous Retroviral Sequences in Human Peripheral Blood Mononuclear Cells
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Epstein-Barr virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking and not mimicking Epstein-Barr virus nuclear antigen-1.
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T lymphocytes in systemic lupus erythematosus: an update
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The Monomeric Guanosine Triphosphatase rab4 Controls an Essential Step on the Pathway of Receptor-mediated Antigen Processing in B Cells
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Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir
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Selective Up-Regulation of Intact, but Not Defective env RNAs of Endogenous Modified Polytropic Retrovirus by the Sgp3 Locus of Lupus-Prone Mice
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Identification of a retinoic acid-inducible endogenous retroviral transcript in the human teratocarcinoma-derived cell line PA-1
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Structure and genomic organization of a novel human endogenous retrovirus family: HERV-K (HML-6).
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Type C RNA virus-specific antibody in human systemic lupus erythematosus demonstrated by enzymoimmunoassay.
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Transcription of Human Endogenous Retroviral Sequences Related to Mouse Mammary Tumor Virus in Human Breast and Placenta: Similar Pattern in Most Malignant and Nonmalignant Breast Tissues*
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B cell epitope on the U1 snRNP‐C autoantigen contains a sequence similar to that of the herpes simplex virus protein
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Interactions of chemical inducers and steroid enhancers of endogenous mouse type-C RNA viruses
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Cloning and sequencing of TT virus genotype 6 and expression of antigenic open reading frame 2 proteins
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The human T-cell leukemia virus-related endogenous sequence (HRES1) is located on chromosome 1 at q42
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FGF-2 antisense RNA encodes a nuclear protein with MutT-like antimutator activity
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A Model for Antigen-Specific T-Cell Anergy: Displacement of CD4-p56 lck Signalosome from the Lipid Rafts by a Soluble, Dimeric Peptide-MHC Class II Chimera
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Selective Defect in Antigen-Induced TCR Internalization at the Immune Synapse of CD8 T Cells Bearing the ZAP-70(Y292F) Mutation
Davanture, S., Leignadier, J., Milani, P., Soubeyran, P., MALISSEN, B., Malissen, M., Schmitt‐Verhulst, A., & Boyer, C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.3140 · Cited by 28 · see citing works
The role of adapter proteins in T cell activation
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Transcripts from a Novel Human KRAB Zinc Finger Gene Contain SplicedAluand Endogenous Retroviral Segments
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Coamplification and Dispersion of Adjacent Human Endogenous Retroviral HERV-H and HERV-E Elements; Presence of Spliced Hybrid Transcripts in Normal Leukocytes
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The Human Transaldolase Gene (TALDO1) Is Located on Chromosome 11 at p15.4–p15.5
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Search for epstein‐barr and type c oncornaviruses in systemic lupus erythematosus
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γδ-T Cell-Receptor-Positive Lymphocytes Inhibit Human Hematopoietic Progenitor Cell Growth in HIV Type 1-Infected Patients
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Phosphatidylinositol synthesis is a proximal event in intracellular signaling coupled to T cell receptor ligation. Differential induction by conventional antigen and retroviral superantigen.
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Human Transaldolase-associated Repetitive Elements Are Transcribed by RNA Polymerase III
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Identification of New Endogenous Retroviral Sequences Belonging to the HERV-W Family in Human Cancer Cells
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Identification of Endogenous Retroviral Sequences Based on Modular Organization: Proviral Structure at the SSAV1 Locus
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Letter to the Editor
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IL-1 induces intracisternal type A virus and retrovirus type C in pancreatic beta-cells of NOD mice.
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Mitochondrial hyperpolarization and ATP depletion in patients with systemic lupus erythematosus
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[13]McGuinnis MH Macher AH Rook AH Red cell autoantibodies in patients with AIDS Transfusion 1986 26 405 409 3765030
[32]Coffin JM Hughes SH Varmus HE Coffin JM Hughes SH Varmus HE Retrotransposons, endogenous retroviruses, and the evolution of retroelements Retroviruses 1997 Cold Spring Harbor Cold Spring Harbor Laboratory Press 343 435 21433351
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[139]Magistrelli C Banki K Ferrante P Perl A Mapping and cloning of polymorphic genotypes of the HRES-1 LTR Arth Rheum 1994 37 S316 10436175

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Authors: Perl, A., Fernandez, D., Telarico, T., & Phillips, P. E.
Affiliations: SUNY Upstate Medical University (US)
Venue: Current Opinion in Rheumatology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-09
Volume: 22
Issue: 5
Pages: 483-492
ISSN: 1040-8711 (ISSN-L)
DOI: 10.1097/bor.0b013e32833c6297
PMC: PMC5314925
OpenAlex: W2078912949
Cited by: 75
References: 150
Citations by year: 2026: 1 · 2025: 4 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 9
FWCI: 0.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Current Opinion in Rheumatology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Allergy and Infectious Diseases (R01AI048079, R01AI122176, R01AI072648, R01-AI48079)
Topics: Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: endogenous retroviruses, systemic lupus erythematosus, lupus pathogenesis, Rab4, CD4 downregulation, chilblain lupus, TREX1, HIV-1 Tat protein, autoantigens, molecular mimicry, interferon, anti-DNA antibodies, autoantibodies
MeSH terms: Humans, Lupus Erythematosus, Systemic, Autoimmunity, Molecular Mimicry, Endogenous Retroviruses

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