The envelope of human endogenous retrovirus in neuro-inflammation
© Dougier et al; licensee BioMed Central Ltd. 2009
Published: 24 September 2009
Several viruses are known to interact with the host defences either to escape from the immune responses or to gain advantage of inflammatory mediators to survive. Human endogenous retroviruses (HERV) are integrated and are estimated represent up to 8% o the human genome. An exogenous virus from HERV. W family was initially isolated from brain cells of patients suffering of multiple sclerosis and named MSRV . Several lines of evidence support that its envelope protein (ENV) or its soluble extra-cellular subunit (ENV-SU) contributes to inflammation associated with the disease: 1) ENV promotes polyclonal expansion of T lymphocytes , 2) ENV-SU induces human monocytes and dendritic cells (DC) to produce inflammatory cytokines through engagement of CD14 and TLR4 .
In order to study in vivo effects of MSRV, mice were treated for experimental allergic encephalitis (EAE) induction, a mouse model for MS, after antigenic myelin peptide immunisation either with complete Freund's adjuvant or ENV-SU. Clinical score showed significant EAE symptoms in both mice but no symptoms in control mice receiving no adjuvant or no ENV (Fig. 1). Cultures of splenocytes from either ENV-SU or adjuvant treated mice, recalled with the myelin antigen, led to IFN-γ production (not shown), indicating T lymphocyte reactivity towards the myelin antigen.
by promoting inflammatory response through CD14/TLR4 pathway, the envelope of MSRV/HERV contributes to EAE in mice and thus may be one of the key actors of MS etiology in humans.
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