title: Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions.
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.
authors.affiliation: bioMérieux, R&D, Chemin de l'Orme, 69280 Marcy L'Etoile, France. herve_perron@eu.biomerieux.com
authors.forename: Hervé
authors.initials: H
authors.lastname: Perron
authors.forename: Françoise
authors.initials: F
authors.lastname: Lazarini
authors.forename: Klemens
authors.initials: K
authors.lastname: Ruprecht
authors.forename: Christine
authors.initials: C
authors.lastname: Péchoux-Longin
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.forename: Véronique
authors.initials: V
authors.lastname: Sazdovitch
authors.forename: Alain
authors.initials: A
authors.lastname: Créange
authors.forename: Nicole
authors.initials: N
authors.lastname: Battail-Poirot
authors.forename: Geneviève
authors.initials: G
authors.lastname: Sibaï
authors.forename: Lyse
authors.initials: L
authors.lastname: Santoro
authors.forename: Michel
authors.initials: M
authors.lastname: Jolivet
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Darlix
authors.forename: Peter
authors.initials: P
authors.lastname: Rieckmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Hauw
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
mesh_terms: D000328:Adult; D000368:Aged; D001921:Brain / Q000821:virology*; D020077:Endogenous Retroviruses; D005260:Female; D015686:Gene Products, env / Q000096:biosynthesis*; D015683:Gene Products, gag / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000821:virology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000821:virology*; D009474:Neurons / Q000821:virology
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag