Ancient Adversary – HERV-K (HML-2) in Cancer

Dervan, Eoin; Bhattacharyya, Dibyangana; McAuliffe, Jake D.; Khan, Faizan Haider; Glynn, Sharon A.

doi:10.3389/fonc.2021.658489

Cited by 31 publications

(33 citation statements)

References 117 publications

(156 reference statements)

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“…Human endogenous retrovirus-K (HERV-K/ERVK) is a genomic symbiont in primates. Specifically, the HERV-K subgroup human mouse mammary tumor virus-like 2 (HML-2) is of particular interest because it is a recent integrant into the human genome and can become reactivated in several disease state, such as neurological disorders, autoimmune disorders and cancer (230).…”

Section: Human Endogenous Retrovirus-k (Herv-k/ervk) and Alsmentioning

confidence: 99%

Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections

et al. 2022

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In this article we review complications to the peripheral nervous system that occur as a consequence of viral infections, with a special focus on complications of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We discuss neuromuscular complications in three broad categories; the direct consequences of viral infection, autoimmune neuromuscular disorders provoked by viral infections, and chronic neurodegenerative conditions which have been associated with viral infections. We also include discussion of neuromuscular disorders that are treated by immunomodulatory therapies, and how this affects patient susceptibility in the current context of the coronavirus disease 2019 (COVID-19) pandemic. COVID-19 is associated with direct consequences to the peripheral nervous system via presumed direct viral injury (dysgeusia/anosmia, myalgias/rhabdomyolysis, and potentially mononeuritis multiplex) and autoimmunity (Guillain Barré syndrome and variants). It has important implications for people receiving immunomodulatory therapies who may be at greater risk of severe outcomes from COVID-19. Thus far, chronic post-COVID syndromes (a.k.a: long COVID) also include possible involvement of the neuromuscular system. Whether we may observe neuromuscular degenerative conditions in the longer term will be an important question to monitor in future studies.

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Section: Human Endogenous Retrovirus-k (Herv-k/ervk) and Alsmentioning

confidence: 99%

Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections

et al. 2022

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“…Since many undifferentiated cancers possess HERV antigens, HERV expression has been suggested as a potential tumor-specific therapeutic target [46,47]. In one study, in tumors with high HML-2 expression, env directed antibody treatment reduced metastasis and tumor growth, while inducing an immunogenic response [48].…”

Section: Endogenous Retroviral Element Expression As a Target For Treatmentmentioning

confidence: 99%

Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors

Doucet-O’Hare

Rosenblum

Shah

et al. 2021

JPM

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Human endogenous retroviruses (HERVs), which are critical to normal embryologic development and downregulated during normal maturation, have been implicated in a variety of cancers. Abnormal persistent production of HERVs has been suggested to play a role in oncogenesis and to confer stem cell properties to cells. We recently demonstrated that the most recently incorporated HERV element (HERV-K HML-2) has been associated with the pathogenesis of the embryonal atypical teratoid rhabdoid tumor (AT/RT), shifting our understanding of embryonal tumor development. HML-2 expression is vital for proper human development and its expression is suppressed via methylation or chromatin remodeling as cells differentiate. We previously found that dysfunctional chromatin remodeling due to loss of SMARCB1 expression induces HML-2 envelope (env) expression, impairing cellular differentiation and migration, and facilitating tumor growth in AT/RT. Epigenetic dysregulation in other embryonal tumors with concomitant expression of stem-cell markers may facilitate HML-2 expression. Future studies could utilize HML-2 as potential diagnostic criteria, use its expression as a treatment biomarker, and investigate the efficacy of therapies targeting cells with high HML-2 expression.

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“…HERVs, and related transposable elements, have been linked to a wide range of diseases including cancer and neurodegeneration via multiple mechanisms. For example, their insertion into the human genome may alter gene expression or disrupt reading frames (9); they were reported to be upregulated in biological samples from people affected by neurodegenerative diseases and cancer (10,11,12) . Furthermore, their expression may be toxic for certain cell types such as motor neurons (13).…”

Section: Introductionmentioning

confidence: 99%

An assessment of bioinformatics tools for the detection of human endogenous retroviral insertions in short-read genome sequencing data

Bowles

Kabiljo

Jones

et al. 2022

Preprint

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There is a growing interest in the study of human endogenous retroviruses (HERVs) given the substantial body of evidence that implicates them in many human diseases. Although their genomic characterization presents numerous technical challenges, next-generation sequencing (NGS) has shown potential to detect HERV insertions and their polymorphisms in humans, and a number of computational tools to detect them in short-read NGS data exist. In order to design optimal analysis pipelines, an independent evaluation of the currently available tools is required. We evaluated the performance of a set of such tools using a variety of experimental designs and types of NGS datasets. These included 50 human short read whole-genome sequencing samples, matching long and short read NGS data, and simulated short-read NGS data. Our results highlight the performance variability of the tools across the datasets and suggest that different tools might be suitable for different study designs. Using multiple tools and a consensus approach is advisable if computationally feasible and wet-lab validation via PCR is advisable where biological samples are available.

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Ancient Adversary – HERV-K (HML-2) in Cancer

Cited by 31 publications

References 117 publications

Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections

Neuromuscular Complications of SARS-CoV-2 and Other Viral Infections

Endogenous Retroviral Elements in Human Development and Central Nervous System Embryonal Tumors

An assessment of bioinformatics tools for the detection of human endogenous retroviral insertions in short-read genome sequencing data

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