POSTER
ENDOGENOUS RETROVIRUS
HERV-W PROTEINS IN HUMAN BRAIN: EVIDENCE FOR PATHOPHYSIOLOGICAL MODULATION OF
GAG AND ENV EXPRESSION IN DEMYELINATING DISEASES
Lazarini F1, Ruprecht K2, Péchoux
C2, Seilhean D3, Sazdovitch V3, A. Créange4,
Battail-Poirot N5, Sibaï
G5, Marcel F5, Souillet Y5, Santoro L5
Jolivet M5, Lassmann H.3, Hauw JJ3, and Perron
H5
A retroviral element (MSRV)
defining a family of genetically-inherited endogenous retroviruses (HERV-W) has
been characterized in cell cultures from patients with multiple sclerosis. The
present immunohistological study was performed by three independent groups using
the same panel of antibodies raised against recombinant MSRV antigens but also
detecting highly conserved HERV-W family proteins. A physiological expression
of HERV-W Env and Gag proteins in normal brain was observed in neuronal cells,
whereas upregulation of HERV-W Gag alone was detected in axonal structures of
demyelinated white matter from patients with Progressive Multifocal
Leukoencephalopathy (PML) and with Multiple Sclerosis (MS). In MS plaque,
HERV-W upregulation was also detected in endothelial cells and in few
microgliocyte-like cells. In parallel, antibodies against another endogenous
retrovirus family (HERV-K) gave constantly negative results in all brain
samples. This multicenter study provides novel physiopathological insights in
diseases such as MS and PML, but also raises questions about a possible
physiological function in normal neurons by analogy with previous reports
involving HERV-W7q Env in placental syncitiotrophoblast fusion ref.
KEY-WORDS: Retrovirus,
HERV-W, Antigen, Brain, Neuron, Axon, Endothelial Cell; microgliocyte, Multiple
Sclerosis, Progressive Multifocal Leucoencephalopathy, demyelination.