Human endogenous retroviruses and the nervous system

Douville, Renée N.; Nath, Avindra

doi:10.1016/b978-0-444-53488-0.00022-5

Cited by 34 publications

(42 citation statements)

References 214 publications

(297 reference statements)

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“…ERVs have been demonstrated to be associated with a variety of neurologic diseases, as reviewed in Douville and Nath (2014). One such disease is amyotrophic lateral sclerosis (ALS).…”

Section: Ervs and Human Diseasementioning

confidence: 99%

Endogenous Retroviruses: With Us and against Us

et al. 2017

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Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe how disruption of the regulated mechanisms of ERVs may impact somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.

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“…ERVs have been demonstrated to be associated with a variety of neurologic diseases, as reviewed in Douville and Nath (2014). One such disease is amyotrophic lateral sclerosis (ALS).…”

Section: Ervs and Human Diseasementioning

confidence: 99%

Endogenous Retroviruses: With Us and against Us

et al. 2017

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“…Although several genetic forms of ALS have been documented, the aetiology of the sporadic form of this pathology remains unknown [1]. Recently, in the pathophysiology of ALS, a possible retroviral implication has been hypothesized since some murine and human retroviruses can cause similar neurodegeneration, and in the serum of patients with sporadic ALS high activity levels of the retroviral enzyme reverse transcriptase (RT) have been demonstrated [2][3][4][5]. In particular, the exogenous retrovirus human T-lymphotropic virus 1 (HTLV-1) has been detected by its RT activity in post-mortem brain tissue of Guamanian ALS patients [6], and human endogenous retroviral (HERV) sequences have been detected in motor neurons and other cells of the central nervous system (CNS) [6].…”

Section: Introductionmentioning

confidence: 99%

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases

Arru

Mameli

Deiana

et al. 2018

Euro J of Neurology

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“…Analysis of RT activity as such does not identify the origin of the enzyme, but the involvement of HERV‐encoded elements has been proposed for HERV‐W (ALS muscle biopsies) , or HERV‐K (ALS post‐mortem brain) . See also and .…”

Section: Hervs As Pathogensmentioning

confidence: 99%

“…In numerous other species, from mice (8,19) to cats (20) to koalas (21), (some) endogenous retroviruses are demonstrably pathogenic, whereas in humans a role for HERVs in the etiology of a number of diseases have been suggested (5,6,(22)(23)(24), but an unequivocal pathogenetic cause-effect relationship is as yet unknown.…”

mentioning

confidence: 99%

Human endogenous retroviruses in neurologic disease

Christensen

2016

APMIS

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Endogenous retroviruses are pathogenic – in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause‐effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV‐H/F and HERV‐W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV‐associated dementia (HAD), indications are accumulating for involvement of the HERV‐K family, and also HERV‐H/F and/or HERV‐W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non‐pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV‐directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential.

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Human endogenous retroviruses and the nervous system

Cited by 34 publications

References 214 publications

Endogenous Retroviruses: With Us and against Us

Endogenous Retroviruses: With Us and against Us

Humoral immunity response to human endogenous retroviruses K/W differentiates between amyotrophic lateral sclerosis and other neurological diseases

Human endogenous retroviruses in neurologic disease

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