Systemic lupus erythematosus and Sjögren's syndrome: Edited by Dr Andras PerlEndogenous retroviral pathogenesis in lupusPerl, Andras; Fernandez, David; Telarico, Tiffany; Phillips, Paul EAuthor Information Division of Rheumatology, Department of Medicine and Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, New York, USA Correspondence to Andras Perl, Division of Rheumatology, Department of Medicine, SUNY, 750 East Adams Street, Syracuse, NY 13210, USA E-mail: [email protected] Current Opinion in Rheumatology: September 2010 - Volume 22 - Issue 5 - p 483-492 doi: 10.1097/BOR.0b013e32833c6297 Buy Metrics 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/TCRζ 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. © 2010 Lippincott Williams & Wilkins, Inc.