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
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.
To characterise the mode of action of ENV in mice, DC were cultured from C57BL/6 bone marrow and incubated with ENV-SU. DC secreted amounts of IL-6 (Fig.
Clinical score follow-up of C57BL/6 mice injected with MOG 35-55 and IFA, CFA or ENV
Clinical score follow-up of C57BL/6 mice injected with MOG 35-55 and IFA, CFA or ENV. Mean values were calculated for each group of mice.
Activation of mouse dendritic cells by the envelope
Activation of mouse dendritic cells by the envelope. Bone marrow derived DC were incubated with either 0.5μg/ml or 1μg/ml of ENV-SU for 24 h and IL-6 was measured by ELISA. Before incubation with the cells, ENV-SU is incubated, or not, with the anti-ENV antibodies during 1 h at 4°C. Control samples are incubated with ENV-SU alone, with LPS or without stimulation (NA).
Activation of mouse dendritic cells by the envelope depends on CD14
Activation of mouse dendritic cells by the envelope depends on CD14. (see legend Fig2). CD14° = CD14 deficient mouse.
Conclusion
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.