Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions.
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| Abstract |
Antigen expression of a human endogenous retrovirus family, HERV-W, in normal human brain and multiple sclerosis lesions was studied by immunohistochemistry by three independent groups. The HERV-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis-associated retroviral element (MSRV). A panel of antibodies against envelope (ENV) and capsid (GAG) antigens was tested. A physiological expression of GAG proteins in neuronal cells was observed in normal brain, whereas there was a striking accumulation of GAG antigen in axonal structures in demyelinated white matter from patients with MS. Prominent HERV-W GAG expression was also detected in endothelial cells of MS lesions from acute or actively demyelinating cases, a pattern not found in any control. A physiological expression of ENV proteins was detected in microglia in normal brain; however,a specific expression in macrophages was apparently restricted to early MS lesions. Thus, converging results from three groups confirm that GAG and ENV proteins encoded by the HERV-W multicopy gene family are expressed in cells of the central nervous system under normal conditions. Similar to HERV-W7q ENV (Syncitin), which is expressed in placenta and has been shown to have a physiological function in syncytio-trophoblast fusion, HERV-W GAG may thus also have a physiological function in human brain. This expression differs in MS lesions, which may either reflect differential regulation of inherited HERV-W copies, or expression of "infectious" MSRV copies. This is compatible with a pathophysiological role in MS, but also illustrates the ambivalence of such HERV antigens, which can be expressed in cell-specific patterns, under physiological or pathological conditions.
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| Authors | Hervé Perron, Françoise Lazarini, Klemens Ruprecht, Christine Péchoux-Longin, Danielle Seilhean, Véronique Sazdovitch, Alain Créange, Nicole Battail-Poirot, Geneviève Sibaï, Lyse Santoro, Michel Jolivet, Jean-Luc Darlix, Peter Rieckmann, Thomas Arzberger, Jean-Jacques Hauw, Hans Lassmann |
| Journal | Journal of neurovirology (J Neurovirol) Vol. 11 Issue 1 Pg. 23-33 (Feb 2005) ISSN: 1355-0284 [Print] United States |
| PMID | 15804956 (Publication Type: Journal Article, Multicenter Study) |
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