Human endogenous retroviruses in the aetiology of MS

Area of Science:

• Neurology
• Immunology
• Virology

Background:

• Multiple sclerosis (MS) is an immune-mediated neurologic disease with suspected links to human endogenous retroviruses (HERVs).
• HERVs are retroviral sequences integrated into the human genome, some of which are implicated in disease pathology in other species.
• Specific HERV families (e.g., HERV-H/F, HERV-W/MSRV) show activation in MS patients' nervous systems and peripheral cells.

Purpose of the Study:

• To explore the association between HERVs and multiple sclerosis.
• To investigate the pathogenic potential of HERV-encoded genes and proteins in MS.
• To highlight the role of regulatory pathways, epigenetics, and restriction factors in HERV activation relevant to MS.

Main Methods:

• Review of existing research on HERV involvement in neurological diseases.
• Analysis of documented HERV family activation in the central nervous system and periphery of MS patients.
• Examination of the potential pathogenic role of HERV envelope proteins (Envs).

Main Results:

• Strong indications of an association between MS and HERVs, particularly specific families like HERV-H/F and HERV-W/MSRV.
• HERV-encoded genes and envelope proteins show strong association with MS and possess pathogenic potential.
• Emerging evidence points to the importance of epigenetic regulation and restriction factors in controlling HERV activation.

Conclusions:

• HERVs are strongly implicated in multiple sclerosis, with specific HERV elements potentially contributing to disease pathogenesis.
• Understanding HERV regulation is crucial for elucidating their role in MS.
• Antiretroviral therapies targeting HERVs represent a promising novel therapeutic strategy for MS, supported by observations in HIV-infected individuals.