Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active multiple sclerosis

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Multiple sclerosis (MS) is an autoimmune disease with suspected environmental triggers, including viral factors.
• Human endogenous retroviruses (HERVs) are genomic elements found in human DNA, implicated in neuroinflammation.
• HERV-Fc1, part of the HERV-H/F family, shows genetic associations with MS, warranting further investigation.

Purpose of the Study:

• To investigate the expression of HERV-H/F Gag protein in peripheral blood mononuclear cells (PBMCs) of MS patients and healthy controls.
• To quantify extracellular HERV-Fc1 RNA viral loads in the plasma of MS patients and healthy controls.
• To explore the potential link between HERV-Fc1 and the pathology of multiple sclerosis.

Main Methods:

• Flow cytometry was used to analyze HERV-H/F Gag protein expression in PBMCs (CD4+ T cells, CD8+ T cells, monocytes).
• SYBR green-based absolute quantitative PCR (Q-PCR) was employed to measure extracellular HERV-Fc1 RNA titers in plasma.
• Comparison of protein and RNA levels between healthy controls and MS patients with active or non-active disease.

Main Results:

• Significant elevation of HERV-H/F Gag protein expression was observed in CD4+ T cells, CD8+ T cells, and monocytes of MS patients with active disease.
• A 4-fold increase in extracellular HERV-Fc1 RNA titers was detected in the plasma of patients with active MS compared to healthy controls.
• These findings indicate a differential expression pattern of HERV-Fc1 components in active MS.

Conclusions:

• The study strengthens the association between HERV-Fc1 and multiple sclerosis pathology.
• Increased HERV-H/F Gag protein and HERV-Fc1 RNA levels in active MS suggest a potential role in disease mechanisms.
• HERV-Fc1 biology presents a promising avenue for understanding MS and potentially other autoimmune disorders.