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Multiple Sclerosis between Genetics and Infections: Human Endogenous Retroviruses in Monocytes and Macrophages
Elena Morandi1, Rachael E Tarlinton2, Bruno Gran1
1Clinical Neurology Research Group, Division of Clinical Neuroscience, School of Medicine, University of Nottingham , Nottingham , UK.
Abstract:
The etiology of multiple sclerosis (MS) is still unknown, but there is strong evidence that genetic predisposition associated with environmental factors can trigger the disease. An estimated 30 million years ago, exogenous retroviruses are thought to have integrated themselves into human germ line cells, becoming part of human DNA and being transmitted over generations. Usually such human endogenous retroviruses (HERVs) are silenced or expressed at low levels, but in some pathological conditions, such as MS, their expression is higher than that in the healthy population. Three HERV families have been associated with MS: HERV-H, HERV-K, and HERV-W. The envelope protein of MS-associated retrovirus (MSRV) from the HERV-W family currently has the strongest evidence as a potential trigger for MS. In addition to expression in peripheral immune cells, MSRV is expressed in monocytes and microglia in central nervous system lesions of people with MS and, through the activation of toll-like receptor 4, it has been shown to drive the production of proinflammatory cytokines, reduction of myelin protein expression, and death of oligodendrocyte precursors. In conclusion, the association between HERVs and MS is well documented and a pathological role for MSRV in MS is plausible. Further studies are required to determine whether the presence of these HERVs is a cause or an effect of immune dysregulation in MS.
Insights
Human endogenous retroviruses (HERVs), particularly MS-associated retrovirus (MSRV), show higher expression in multiple sclerosis (MS) and may trigger disease progression. Further research is needed to confirm if HERVs cause or result from MS immune dysregulation.
Area of Science:
- Neuroimmunology
- Virology
- Genetics
Background:
- The exact cause of multiple sclerosis (MS) remains unknown, though genetic and environmental factors are implicated.
- Human endogenous retroviruses (HERVs) are ancient viral sequences integrated into the human genome, typically silenced but sometimes reactivated in disease states.
- Elevated HERV expression is observed in MS patients compared to healthy individuals.
Purpose of the Study:
- To investigate the association between human endogenous retroviruses (HERVs) and the etiology of multiple sclerosis (MS).
- To evaluate the potential role of MS-associated retrovirus (MSRV) as a trigger for MS pathogenesis.
Main Methods:
- Analysis of HERV expression levels in MS patients versus healthy controls.
- Investigation of MSRV expression in central nervous system lesions.
- Examination of MSRV's molecular mechanisms, including toll-like receptor 4 activation and downstream effects.
Main Results:
- Three HERV families (HERV-H, HERV-K, HERV-W) are linked to MS.
- MS-associated retrovirus (MSRV) from the HERV-W family shows strong association with MS.
- MSRV expression in CNS lesions correlates with proinflammatory cytokine production, reduced myelin protein, and oligodendrocyte precursor cell death.
Conclusions:
- A significant association between HERVs and MS is well-documented.
- A plausible pathological role for MSRV in MS development and progression exists.
- Further studies are essential to ascertain whether HERVs are a cause or consequence of MS-related immune dysregulation.
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