Quantitative Analysis of Human Endogenous Retrovirus-W env in Neuroinflammatory Diseases

Abstract

Although human endogenous retroviruses (HERVs) constitute 8% of the human genome, their role(s) in health and disease remain uncertain. Nonetheless, increased HERV gene activity has been reported in neuroinflammatory diseases such as multiple sclerosis (MS). The human endogenous retrovirus (HERV)-W7q envelope gene encodes a glycosylated envelope protein, syncytin-1, which is expressed in many tissues. Analysis of HERV envelopes (env) revealed a selectively increased abundance of syncytin-1 encoding RNA in brains from patients with MS (p < 0.01) relative to non-MS patients. However, HERV env expression from blood-derived leukocytes did not differ between groups. A quantitative PCR-based assay for syncytin-1 RNA showed that median viral RNA levels were higher in brains of MS patients (5.0 log₁₀ copies/µg RNA) relative to non-MS patients (4.6 log₁₀ copies/µg RNA) (p < 0.05). Median syncytin-1 DNA levels in MS brains (9.8 log₁₀/µg DNA) were higher than non-MS brain tissue (7.9 log₁₀/µg DNA) (p < 0.001) without evidence of new integration events. In contrast, there were no differences in syncytin-1 RNA copy numbers between groups in both CSF(non-MS: 5.0 log₁₀/ml versus MS: 3.8 log₁₀/ml) and plasma (non-MS: 5.033 log₁₀/ml versus MS: 2.9 log₁₀/ml). These observations emphasize the selective induction of syncytin-1 in brain tissue of MS patients but also illustrate the complex dynamics of this retroelement in neuroinflammatory processes.