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Updated: Feb 23, 2026
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Published on: November 2, 2013
Analysis of Human Endogenous Retrovirus Expression in Multiple Sclerosis Plaques
P J Bhetariya1, J D Kriesel1, K F Fischer2
1Department of Internal Medicine, Division of Infectious Diseases, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Background:
It has been suggested that Human endogenous retroviruses (HERVs) are associated with multiple sclerosis (MS) pathogenesis. The objective of this study was to broadly evaluate the expression of HERV core (GAG) and envelope (ENV) genes in diseased brain white matter samples from MS patients compared to normal controls.
Methods:
Twenty-eight HERV GAG and 88 ENV gene sequences were retrieved, classified by phylogeny, and grouped into clades. Consensus qPCR primers were designed for each clade, and quantitative PCR was performed on 33 MS and 9 normal control frozen brain samples. MS samples included chronic progressive (n=5), primary progressive (n=4), secondary progressive (n=14), relapsing remitting (n=3) and unclassified confirmed MS cases (n=7). The levels of GAG and ENV RNA within each of the samples were quantitated and normalized using the neuronal reference gene RPL19. Expression differences were analyzed for MS vs control.
Results:
Expression of GAG clades 1A, 3B, and 3C mapping to HERV-E and HERV-K were significantly increased compared to controls, while GAG clade 3A expression was decreased. Expression of HERV ENV clades 2, 3A, 3B, mapping to RTVL, HERV-E and HERV-K and MSRV (HERV-W), were significantly increased in the MS group. However, the relative expression differences between the MS and control groups were small, differing less than 1.5-fold.
Conclusion:
Expression of GAG and ENV mapping to HERV-E, RTVL and HERV-K10 families were significantly increased in the MS group. However, the relative expression differences between the MS and control groups were small, differing less than 1.5-fold. These results indicate that the expression of HERV GAG and ENV regions do not differ greatly between MS and controls in these frozen brain samples.
Insights
Human endogenous retroviruses (HERVs) GAG and ENV gene expression showed slight increases in multiple sclerosis (MS) brain samples. However, these differences were minimal, suggesting HERVs may not be a major driver of MS pathogenesis.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Genetics
Background:
- Human endogenous retroviruses (HERVs) are implicated in multiple sclerosis (MS) pathogenesis.
- This study investigates HERV GAG and ENV gene expression in MS brain tissue.
Purpose of the Study:
- To evaluate the expression levels of HERV GAG and ENV genes in the brain white matter of MS patients.
- To compare HERV gene expression in MS samples with normal brain controls.
Main Methods:
- Quantitative PCR (qPCR) was used to measure GAG and ENV RNA levels in 33 MS and 9 control brain samples.
- Primers were designed for 28 HERV GAG and 88 ENV gene sequences, grouped by phylogenetic clades.
- Gene expression was normalized to the RPL19 reference gene and analyzed for differences between MS and control groups.
Main Results:
- Expression of specific GAG clades (1A, 3B, 3C) mapping to HERV-E and HERV-K was significantly increased in MS samples.
- Expression of HERV ENV clades (2, 3A, 3B) mapping to RTVL, HERV-E, HERV-K, and HERV-W was also significantly increased in MS.
- However, the fold-change differences in expression between MS and control groups were small, less than 1.5-fold.
Conclusions:
- HERV-E, RTVL, and HERV-K10 family GAG and ENV genes showed significantly increased expression in MS brain samples.
- The observed expression differences between MS and control groups were minor, indicating limited contribution of these HERV regions.
- These findings suggest that HERV GAG and ENV expression does not substantially differ between MS patients and controls in the studied brain samples.
