Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
- PMID: 27211560
- PMCID: PMC4856744
- DOI: 10.1016/j.ebiom.2016.03.001
Human Endogenous Retrovirus and Neuroinflammation in Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Abstract
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.
Keywords: CIDP; Endogenous retrovirus; GNbAC1; HERV; HERV-W; MSRV; Peripheral neuropathies; Schwann cell.
Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.
Figures
![Fig. 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4856744/bin/gr1.gif)
![Fig. 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4856744/bin/gr2.gif)
![Fig. 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4856744/bin/gr3.gif)
![Fig. 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4856744/bin/gr4.gif)
![Fig. 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4856744/bin/gr5.gif)
Comment in
-
Novel Therapeutic Avenues for Chronic Inflammatory Demyelinating Polyneuropathy: The Difficulties of Disease Diversity.EBioMedicine. 2016 Apr;6:12-13. doi: 10.1016/j.ebiom.2016.03.026. Epub 2016 Mar 19. EBioMedicine. 2016. PMID: 27211536 Free PMC article. No abstract available.
Similar articles
-
Preclinical and early clinical development of GNbAC1, a humanized IgG4 monoclonal antibody targeting endogenous retroviral MSRV-Env protein.MAbs. 2015;7(1):265-75. doi: 10.4161/19420862.2014.985021. MAbs. 2015. PMID: 25427053 Free PMC article. Clinical Trial.
-
MSRV envelope protein is a potent, endogenous and pathogenic agonist of human toll-like receptor 4: Relevance of GNbAC1 in multiple sclerosis treatment.J Neuroimmunol. 2016 Feb 15;291:29-38. doi: 10.1016/j.jneuroim.2015.12.006. Epub 2015 Dec 11. J Neuroimmunol. 2016. PMID: 26857492
-
Treatment against human endogenous retrovirus: a possible personalized medicine approach for multiple sclerosis.Mol Diagn Ther. 2015 Oct;19(5):255-65. doi: 10.1007/s40291-015-0166-z. Mol Diagn Ther. 2015. PMID: 26376649
-
A new therapeutic approach for type 1 diabetes: Rationale for GNbAC1, an anti-HERV-W-Env monoclonal antibody.Diabetes Obes Metab. 2018 Sep;20(9):2075-2084. doi: 10.1111/dom.13357. Epub 2018 Jun 10. Diabetes Obes Metab. 2018. PMID: 29749030 Review.
-
The aliens inside human DNA: HERV-W/MSRV/syncytin-1 endogenous retroviruses and neurodegeneration.J Infect Dev Ctries. 2015 Jul 4;9(6):577-87. doi: 10.3855/jidc.6916. J Infect Dev Ctries. 2015. PMID: 26142666 Review.
Cited by
-
SARS-CoV-2 awakens ancient retroviral genes and the expression of proinflammatory HERV-W envelope protein in COVID-19 patients.iScience. 2023 May 19;26(5):106604. doi: 10.1016/j.isci.2023.106604. Epub 2023 Apr 7. iScience. 2023. PMID: 37091988 Free PMC article.
-
HERV1-env Induces Unfolded Protein Response Activation in Autoimmune Liver Disease: A Potential Mechanism for Regulatory T Cell Dysfunction.J Immunol. 2023 Mar 15;210(6):732-744. doi: 10.4049/jimmunol.2100186. J Immunol. 2023. PMID: 36722941 Free PMC article.
-
Reviewing the Potential Links between Viral Infections and TDP-43 Proteinopathies.Int J Mol Sci. 2023 Jan 13;24(2):1581. doi: 10.3390/ijms24021581. Int J Mol Sci. 2023. PMID: 36675095 Free PMC article. Review.
-
Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections.Front Neurol. 2022 Jun 24;13:914411. doi: 10.3389/fneur.2022.914411. eCollection 2022. Front Neurol. 2022. PMID: 35812094 Free PMC article. Review.
-
Endogenous Retroviruses (ERVs): Does RLR (RIG-I-Like Receptors)-MAVS Pathway Directly Control Senescence and Aging as a Consequence of ERV De-Repression?Front Immunol. 2022 Jun 9;13:917998. doi: 10.3389/fimmu.2022.917998. eCollection 2022. Front Immunol. 2022. PMID: 35757716 Free PMC article. Review.
References
-
- Anon. Recommendations on diagnostic strategies for chronic inflammatory demyelinating polyradiculoneuropathy. J. Neurol. Neurosurg. Psychiatry. 2008;79(2):115–118. - PubMed
-
- Anon. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society—First Revision. J. Peripher. Nerv. Syst. 2010;15(1):1–9. - PubMed
-
- Belshaw R., Katzourakis A., Paces J., Burt A., Tristem M. High copy number in human endogenous retrovirus families is associated with copying mechanisms in addition to reinfection. Mol. Biol. Evol. 2005;22(4):814–817. - PubMed
-
- Bonnaud B., Bouton O., Oriol G., Cheynet V., Duret L., Mallet F. Evidence of selection on the domesticated ERVWE1 env retroviral element involved in placentation. Mol. Biol. Evol. 2004;21(10):1895–1901. - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources