Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions.
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.
Perron
Hervé
H
bioMérieux, R&D, Chemin de l'Orme, 69280 Marcy L'Etoile, France. herve_perron@eu.biomerieux.com
Lazarini
Françoise
F
Ruprecht
Klemens
K
Péchoux-Longin
Christine
C
Seilhean
Danielle
D
Sazdovitch
Véronique
V
Créange
Alain
A
Battail-Poirot
Nicole
N
Sibaï
Geneviève
G
Santoro
Lyse
L
Jolivet
Michel
M
Darlix
Jean-Luc
JL
Rieckmann
Peter
P
Arzberger
Thomas
T
Hauw
Jean-Jacques
JJ
Lassmann
Hans
H
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
D015686:Gene Products, env; D015683:Gene Products, gag