title: Endogenous retroviral pathogenesis in lupus.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Rheumatology, Department of Medicine and Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA. perla@upstate.edu
authors.forename: Andras
authors.initials: A
authors.lastname: Perl
authors.forename: David
authors.initials: D
authors.lastname: Fernandez
authors.forename: Tiffany
authors.initials: T
authors.lastname: Telarico
authors.forename: Paul E
authors.initials: PE
authors.lastname: Phillips
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D020077:Endogenous Retroviruses / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology / Q000821:virology*; D018716:Molecular Mimicry