Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus

Molecular Immunology
Kristin A FentonOle Petter Rekvig

Abstract

We have demonstrated that glomerular expression of polyomavirus large T antigen (T-ag) in a binary tetracycline-regulated T-ag transgenic mouse model (i) terminated tolerance for nucleosomes, (ii) released complexes of nucleosomes and T-ag to the microenvironment from dead cells, and (iii) that these complexes bound induced anti-nucleosome antibodies and finally (iv) that they associated with glomerular membranes as immune complexes. This process may be relevant for human lupus nephritis, since productive polyomavirus infection is associated with this organ manifestation. Here, we compare nephritis in the T-ag transgenic mouse with nephritis in human SLE. Glomerular sections were analysed by transmission electron microscopy, immune electron microscopy (IEM) and by co-localization IEM and TUNEL IEM assays to compare morphological changes, composition of immune complexes and formation of nucleosome-T-ag complexes. Affinity of nucleosome-T-ag complexes for glomerular collagen IV and laminin was determined by surface plasmon resonance (SPR). Analyses revealed electron dense structures in both human and murine kidney samples. These EDS were shown to contain T-ag, DNA and histones, indicating that extra-cellular chromatin may origina...Continue Reading

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Citations

Nov 11, 2009·PloS One·Antoine DissetRabary Rajerison
Jun 12, 2013·Molecular Medicine·Natalya SeredkinaOle Petter Rekvig
Dec 18, 2009·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Aug 22, 2015·Pediatric Rheumatology Online Journal·Nirupama GuptaRenee F Modica
Oct 19, 2012·The Tohoku Journal of Experimental Medicine·Pornpimol RianthavornYong Poovorawan

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