Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders

Human endogenous retroviruses (HERVs) are genetic elements resulting from relics of ancestral infection of germline cells, now recognized as cofactors in the etiology of several complex diseases. Here we present a review of findings supporting the role of the abnormal HERVs activity in neurodevelopmental disorders. The derailment of brain development underlies numerous neuropsychiatric conditions, likely starting during prenatal life and carrying on during subsequent maturation of the brain. Autism spectrum disorders, attention deficit hyperactivity disorders, and schizophrenia are neurodevelopmental disorders that arise clinically during early childhood or adolescence, currently attributed to the interplay among genetic vulnerability, environmental risk factors, and maternal immune activation. The role of HERVs in human embryogenesis, their intrinsic responsiveness to external stimuli, and the interaction with the immune system support the involvement of HERVs in the derailed neurodevelopmental process. Although definitive proofs that HERVs are involved in neurobehavioral alterations are still lacking, both preclinical models and human studies indicate that the abnormal expression of ERVs could represent a neurodevelopmental disorders-associated biological trait in affected individuals and their parents.

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The Role of Human Endogenous Retroviruses (HERV-K) in the Pathogenesis of Human Cancers

Molecular Biology ◽

10.4172/2168-9547.1000169 ◽

2016 ◽

Vol 05 (03) ◽

Cited By ~ 3

Author(s):

William Simmons

Keyword(s):

Endogenous Retroviruses ◽

Human Endogenous Retroviruses ◽

Human Cancers

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The epigenetic regulation of synaptic genes contributes to the etiology of autism

Reviews in the Neurosciences ◽

10.1515/revneuro-2021-0014 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Annamaria Srancikova ◽

Zuzana Bacova ◽

Jan Bakos

Keyword(s):

Epigenetic Regulation ◽

Neurodevelopmental Disorders ◽

Autism Spectrum ◽

Prader Willi Syndrome ◽

Epigenetic Mechanisms ◽

Substantial Evidence ◽

Autistic Symptoms ◽

Spectrum Disorders ◽

The Brain

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.

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The role of human endogenous retroviruses in melanoma

British Journal of Dermatology ◽

10.1111/j.1365-2133.2009.09415.x ◽

2009 ◽

Vol 161 (6) ◽

pp. 1225-1231 ◽

Cited By ~ 21

Author(s):

S. Singh ◽

S. Kaye ◽

M.E. Gore ◽

M.O. McClure ◽

C.B. Bunker

Keyword(s):

Endogenous Retroviruses ◽

Human Endogenous Retroviruses

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Role of Copy Number Variations in ADHD

10.5772/intechopen.94383 ◽

2020 ◽

Author(s):

Danijela Krgović

Keyword(s):

Autism Spectrum Disorder ◽

Attention Deficit ◽

Neurodevelopmental Disorders ◽

Copy Number ◽

Autism Spectrum ◽

Copy Number Variations ◽

Spectrum Disorder ◽

Genetic Diagnostics ◽

Healthy Controls

Copy number variations (CNV) have an important role in etiology of neurodevelopmental disorders (NDD). Among them, individuals with attention-deficit and hyperactivity disorders (ADHD) have 1.33 times higher overall rate of CNVs larger than 100 kb compared to healthy controls. These CNVs are often shared with other NDDs and neuropsychiatric disorders such as schizophrenia (SCZ) and autism spectrum disorder (ASD), although duplications of 15q13.3 and 16p13.11 have been found enriched in ADHD cohorts. CNVs provide new opportunities for studying and management of psychiatric disorders including ADHD. Therefore this chapter provides a brief overview of the literature on this topic and presents the benefits of CNV genetic diagnostics in ADHD patients.

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Sensory Reactivity Phenotype in Phelan–McDermid Syndrome Is Distinct from Idiopathic ASD

Genes ◽

10.3390/genes12070977 ◽

2021 ◽

Vol 12 (7) ◽

pp. 977

Author(s):

Teresa Tavassoli ◽

Christina Layton ◽

Tess Levy ◽

Mikaela Rowe ◽

Julia George-Jones ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Potential Role ◽

Autism Spectrum ◽

Typically Developing ◽

Sensory Assessment ◽

Sensory Reactivity ◽

Dsm 5 ◽

Main Driver ◽

Insight Into

Phelan–McDermid syndrome (PMS) is one of the most common genetic forms of autism spectrum disorder (ASD). While sensory reactivity symptoms are widely reported in idiopathic ASD (iASD), few studies have examined sensory symptoms in PMS. The current study delineates the sensory reactivity phenotype and examines genotype–phenotype interactions in a large sample of children with PMS. Sensory reactivity was measured in a group of 52 children with PMS, 132 children with iASD, and 54 typically developing (TD) children using the Sensory Assessment for Neurodevelopmental Disorders (SAND). The SAND is a clinician-administered observation and corresponding caregiver interview that captures sensory symptoms based on the DSM-5 criteria for ASD. Children with PMS demonstrated significantly greater hyporeactivity symptoms and fewer hyperreactivity and seeking symptoms compared to children with iASD and TD controls. There were no differences between those with Class I deletions or sequence variants and those with larger Class II deletions, suggesting that haploinsufficiency of SHANK3 is the main driver of the sensory phenotype seen in PMS. The syndrome-specific sensory phenotype identified in this study is distinct from other monogenic forms of ASD and offers insight into the potential role of SHANK3 deficiency in sensory reactivity. Understanding sensory reactivity abnormalities in PMS, in the context of known glutamatergic dysregulation, may inform future clinical trials in the syndrome.

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The role of Human Endogenous Retroviruses (HERVs) in Multiple Sclerosis and the plausible interplay between HERVs, Epstein–Barr virus infection, and vitamin D

Multiple Sclerosis and Related Disorders ◽

10.1016/j.msard.2021.103318 ◽

2021 ◽

pp. 103318

Author(s):

Tayebeh Latifi ◽

Arghavan Zebardast ◽

Sayed Mahdi Marashi

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Epstein Barr Virus ◽

Endogenous Retroviruses ◽

Epstein Barr Virus Infection ◽

Human Endogenous Retroviruses ◽

Barr Virus ◽

Epstein Barr ◽

Barr Virus Infection

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Role of Human Endogenous Retroviruses in Lymphoma Pathogenesis and a Possible Biomarker of Disease

Blood ◽

10.1182/blood.v112.11.3751.3751 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3751-3751 ◽

Cited By ~ 2

Author(s):

Scott D. Gitlin ◽

Rafael Contreras- Galindo ◽

Mark H. Kaplan ◽

David M. Markovitz

Keyword(s):

Human Genome ◽

Cell Lines ◽

Endogenous Retroviruses ◽

Human Endogenous Retrovirus ◽

Hiv Positive ◽

Human Endogenous Retroviruses ◽

Viral Expression ◽

Very High

Abstract Actively replicating retroviruses entered hominid species millions of years ago and through mutations preventing replication now exist as 8% of the human genome. Active retroviral particles and antigens from the supposedly dormant human endogenous retrovirus, HERV-K (HML2), have been identified in several cancer cell lines. We have recently demonstrated very high RNA titers of HERV-K (HML2) in the plasma of HIV positive individuals by nucleic acid sequence-based amplification (NASBA) and RT-PCR. We now demonstrate very high HERV-K (HML2) RNA titers in the plasma of patients with HIV positive and HIV negative non-Hodgkin lymphoma (NHL) and in Hodgkin Disease (HD), but not in normal individuals. Different copies of HERV-K (HML-2) present throughout the human genome exist as Type 1 viruses which encode a new oncoprotein, NP9, or as Type 2 viruses which encode a functional envelope (env) and express the Rec oncoprotein. Both Types 1 and 2 viruses appear in NHLs but only Type 1 appears in the plasma of those with HD. HERV-K (HML2) Env and Gag proteins, Env and Gag RNA, and Reverse Transcriptase (RT) activity are isolated from patients with a variety of NHLs, but not in normal controls or in patients with non-malignant diseases. Viral titers dramatically decrease, up to an approximately 7.5 log drop, when patients with NHL or HD go into remission following treatment. To further establish the presence of functional viruses in NHL and HD, immuno-gold electron microscopy allowed demonstration of HERV-K (HML2) particles in the plasma of lymphoma patients. Preliminary analysis of the effect of antiretroviral agents on cell lines infected with HERV-K (HML2) demonstrate a drug class-specific reduction in viral expression at drug concentration levels that range from 0.125 – 1 mcg/mL. In conclusion, we have demonstrated evidence that human endogenous retroviruses are found in the plasma of patients with NHL and HD, suggesting that these viruses, previously presumed to be inactive, may play a role in lymphoma pathogenesis. The observation that viral expression parallels declines in disease activity with treatment of disease may allow use of HERV-K (HML2) expression as a biomarker of lymphoma activity. The role of the HERV-K (HML2)-encoded oncoproteins in disease pathogenesis is under study, as is the potential role of antiretroviral therapy for these malignancies.

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The Relationship of the Mechanisms of the Pathogenesis of Multiple Sclerosis and the Expression of Endogenous Retroviruses

Biology ◽

10.3390/biology9120464 ◽

2020 ◽

Vol 9 (12) ◽

pp. 464

Author(s):

Vera R. Lezhnyova ◽

Ekaterina V. Martynova ◽

Timur I. Khaiboullin ◽

Richard A. Urbanowicz ◽

Svetlana F. Khaiboullina ◽

...

Keyword(s):

Multiple Sclerosis ◽

Viral Infections ◽

Endogenous Retroviruses ◽

Epigenetic Mechanisms ◽

Humoral Factors ◽

Human Endogenous Retroviruses ◽

Relationship Of ◽

The Relationship

Two human endogenous retroviruses of the HERV-W family can act as cofactors triggering multiple sclerosis (MS): MS-associated retrovirus (MSRV) and ERVWE1. Endogenous retroviral elements are believed to have integrated in our ancestors’ DNA millions of years ago. Their involvement in the pathogenesis of various diseases, including neurodegenerative pathologies, has been demonstrated. Numerous studies have shown a correlation between the deterioration of patients’ health and increased expression of endogenous retroviruses. The exact causes and mechanisms of endogenous retroviruses activation remains unknown, which hampers development of therapeutics. In this review, we will summarize the main characteristics of human endogenous W retroviruses and describe the putative mechanisms of activation, including epigenetic mechanisms, humoral factors as well as the role of the exogenous viral infections.

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