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Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Raphaël Faucard1, Alexandra Madeira1, Nadège Gehin1
1GeNeuro Innovation, France.
Background:
Human endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects.
Methods:
50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs).
Findings:
In both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env.
Interpretation:
The present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1 may offer new perspectives for treating CIDP patients with positive detection of MSRV-Env expression.
Funding:
Geneuro-Innovation, France.
Insights
Human endogenous retroviruses W (HERV-W) protein MSRV-Env is elevated in chronic inflammatory demyelinating polyradiculoneuropathies (CIDP). This protein drives inflammation in Schwann cells, suggesting MSRV-Env as a therapeutic target for CIDP.
Area of Science:
- Neuroimmunology
- Retroviral research
Background:
- Human endogenous retroviruses W (HERV-W) encode MSRV-Env, a pro-inflammatory protein implicated in Multiple Sclerosis.
- MSRV-Env is detected in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDP), but not in neurological controls.
Purpose of the Study:
- To investigate MSRV expression in CIDP patients.
- To evaluate the pathogenic effects of MSRV-Env in CIDP.
Main Methods:
- Quantified MSRV-env, -pol transcripts, IL6, and CXCL10 in 50 CIDP patients, 19 other neurological disorders (ONDs), and 65 healthy blood donors (HBDs).
- Performed MSRV-Env immunohistology on nerve biopsies from CIDP and control groups.
- Assayed MSRV-Env effects on cultured primary human Schwann cells (HSCs).
Main Results:
- MSRV-env, -pol transcripts, IL6, and CXCL10 were significantly elevated in CIDP patients compared to HBDs and ONDs.
- MSRV-Env protein was detected in Schwann cells of 5/7 CIDP biopsies.
- MSRV-Env exposure increased IL6 and CXCL10 in HSCs, effects inhibited by the neutralizing antibody GNbAC1.
Conclusions:
- MSRV-Env may trigger immune mediator release contributing to CIDP pathophysiology.
- MSRV-Env expression in CIDP patients suggests a role in Schwann cell dysfunction.
- Targeting MSRV-Env with neutralizing antibodies like GNbAC1 may offer new therapeutic strategies for CIDP.
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