Retroviral envelope proteins: Involvement in neuropathogenesis

Hansen, Dorte Tranberg; Petersen, Thor; Christensen, Tove

doi:10.1016/j.jns.2017.07.027

Cited by 17 publications

(19 citation statements)

References 232 publications

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“…It is presently not known whether the activated HERVs primarily contribute to driving the inflammation in MS or vice versa, however, it is established that monocyte activation/differentiation impacts retroviral activation . Numerous factors (notably concurrent activity of members of the herpesvirus family and cytokines) interacts with HERV expression, and it is also established that HERV Env antigens, as such, have pathogenic potential . Notably, at the level of epigenetic regulation, it has been shown that at least parts of the transcriptional reactivations inherent in MS pathogenesis may be explained by a deficiency in a specific mechanism involving heterochromatin protein HP1a for transcriptional repression .…”

Section: Discussionmentioning

confidence: 99%

“…60 Numerous factors (notably concurrent activity of members of the herpesvirus family and cytokines) interacts with HERV expression, 61 and it is also established that HERV Env antigens, as such, have pathogenic potential. 62 Notably, at the level of epigenetic regulation, it has been shown that at least parts of the transcriptional reactivations inherent in MS pathogenesis may be explained by a deficiency in a specific mechanism involving heterochromatin protein HP1a for transcriptional repression. 63 This has also been found to be responsible for the de-repressing activity of promoters of both certain HERVs and proinflammatory cytokines such as TNF-a.…”

Section: Discussionmentioning

confidence: 99%

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Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

et al. 2017

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Multiple sclerosis (MS) is an immune mediated, inflammatory and demyelinating disease of the central nervous system (CNS). Substantial evidence points toward monocytes and macrophages playing prominent roles early in disease, mediating both pro‐ and anti‐inflammatory responses. Monocytes are subdivided into three subsets depending on the expression of CD14 and CD16, representing different stages of inflammatory activation. To investigate their involvement in MS, peripheral blood mononuclear cells from 40 patients with incipient or progressed MS and 20 healthy controls were characterized ex vivo. In MS samples, we demonstrate a highly significant increase in nonclassical monocytes (CD14+CD16++), with a concomitant significant reduction in classical monocytes (CD14++CD16−) compared with healthy controls. Also, a significant reduction in the surface expression of CD40, CD163, and CD192 was found, attributable to the upregulation of the nonclassical monocytes. In addition, significantly increased levels of human endogenous retrovirus (HERV) envelope (Env) epitopes, encoded by both HERV‐H/F and HERV‐W, were specifically found on nonclassical monocytes from patients with MS; emphasizing their involvement in MS disease. In parallel, serum and cerebrospinal fluid (CSF) samples were analyzed for soluble biomarkers of inflammation and neurodegeneration. For sCD163 versus CD163, no significant correlations were found, whereas highly significant correlations between levels of soluble neopterine and the intermediate monocyte (CD14++CD16+) population was found, as were correlations between levels of soluble osteopontin and the HERV Env expression on nonclassical monocytes. The results from this study emphasize the relevance of further focus on monocyte subsets, particularly the nonclassical monocytes in monitoring of inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

et al. 2017

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“…This process is called 'molecular mimicry' (7). Additionally, the HERV encoded proteins may act as superantigens (8,9), and HERV encoded proteins may have neuropathogenic potential (10). Initial evidence for the possible involvement of HERVs in MS was suggested by Perron et al in 1991 (11, 12) and by Christensen et al (13,14), but there has been no conclusive evidence.…”

Section: A C C E P T E D Mmentioning

confidence: 99%

A phase II baseline versus treatment study to determine the efficacy of raltegravir (Isentress) in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium-enhanced MRI: The INSPIRE study

Gold

Marta

Meier

et al. 2018

Multiple Sclerosis and Related Disorders

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Raltegravir did not have any impact on MS disease activity. This could be due to the choice of antiretroviral agent used in this study, the need for a combination of agents, as used in treating HIV infection, the short treatment period or dosing regimen, or the lack of a role of HERV expression in MS once the disease is established. Borderline significance for the association between EBV shedding and the total number of lesions, probably driven by new lesion development, may indicate EBV shedding as a marker of inflammatory disease activity. In conclusion, interesting correlations between HERV-W markers, EBV shedding and new MRI lesions, independent from treatment effects, were found.

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“…Indeed, some think that it is the Env protein of HERV itself that is neuropathogenic (11,42) similarly to what research on other retroviral Env proteins has shown (42,43). There are currently efforts to develop an antibody that specifically targets HERV Env (44), which could also potentially be able to block viral cell infection (45).…”

Section: Mechanismsmentioning

confidence: 97%

ALSUntangled 45: Antiretrovirals

2018

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Retroviral envelope proteins: Involvement in neuropathogenesis

Cited by 17 publications

References 232 publications

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

Subsets of activated monocytes and markers of inflammation in incipient and progressed multiple sclerosis

A phase II baseline versus treatment study to determine the efficacy of raltegravir (Isentress) in preventing progression of relapsing remitting multiple sclerosis as determined by gadolinium-enhanced MRI: The INSPIRE study

ALSUntangled 45: Antiretrovirals

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