The role of human endogenous retroviruses in brain development and function

Apmis ◽  
2016 ◽  
Vol 124 (1-2) ◽  
pp. 105-115 ◽  
Author(s):  
Kristien Mortelmans ◽  
Feng Wang-Johanning ◽  
Gary L. Johanning
Keyword(s):  
Brain Development ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
And Function

scholarly journals Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

2021 ◽  
Author(s):  
Rachel L. Leon ◽  
Imran N. Mir ◽  
Christina L. Herrera ◽  
Kavita Sharma ◽  
Catherine Y. Spong ◽  
...  
Keyword(s):  
Brain Development ◽  
Congenital Heart ◽  
Fetal Brain ◽  
In Utero ◽  
Structure And Function ◽  
Brain Growth ◽  
Neurodevelopmental Outcomes ◽  
Fetal Brain Development ◽  
And Function

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

scholarly journals Endogenous Retroviruses Activity as a Molecular Signature of Neurodevelopmental Disorders

2019 ◽  
Vol 20 (23) ◽  
pp. 6050 ◽  
Author(s):  
Balestrieri ◽  
Matteucci ◽  
Cipriani ◽  
Grelli ◽  
Ricceri ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Autism Spectrum ◽  
Endogenous Retroviruses ◽  
Molecular Signature ◽  
System Support ◽  
Human Endogenous Retroviruses ◽  
Biological Trait ◽  
Attention Deficit Hyperactivity Disorders ◽  
External Stimuli

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.

scholarly journals MicroRNAs in brain development and cerebrovascular pathophysiology

2019 ◽  
Vol 317 (1) ◽  
pp. C3-C19 ◽  
Author(s):  
Qingyi Ma ◽  
Lubo Zhang ◽  
William J. Pearce
Keyword(s):  
Brain Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Great Promise ◽  
Ischemic Brain ◽  
Neural Lineage ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
And Function

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via base-paring with complementary sequences of the 3′-untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology. We review recent progress of the miRNA-based mechanisms in neuronal and cerebrovascular development as well as their role in hypoxic-ischemic brain injury. These findings hold great promise, not just for deeper understanding of basic brain biology but also for building new therapeutic strategies for prevention and treatment of pathologies such as cerebral ischemia.

scholarly journals Zscan4c activates endogenous retrovirus MERVL and cleavage embryo genes

2019 ◽  
Author(s):  
Weiyu Zhang ◽  
Fuquan Chen ◽  
Ruiqing Chen ◽  
Dan Xie ◽  
Jiao Yang ◽  
...  
Keyword(s):  
Developmental Stages ◽  
Embryonic Stem ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Enhancer Activity ◽  
Cell Cleavage ◽  
Cell Embryo ◽  
And Function ◽  
Scan Domain

AbstractEndogenous retroviruses (ERVs) contribute to ∼10 percent of the mouse genome. They are often silenced in differentiated somatic cells but differentially expressed at various embryonic developmental stages. A minority of mouse embryonic stem cells (ESCs), like 2-cell cleavage embryos, highly express ERV MERVL. However, the role of ERVs and mechanism of their activation in these cells are still poorly understood. In this study, we investigated the regulation and function of the stage-specific expressed ERVs, with a particular focus on the totipotency marker MT2/MERVL. We show that the transcription factor Zscan4c functions as an activator of MT2/MERVL and 2-cell/4-cell embryo genes. Zinc finger domains of Zscan4c play an important role in this process. In addition, Zscan4c interacts with MT2 and regulates MT2-nearby 2-cell/4-cell genes through promoting enhancer activity of MT2. Furthermore, MT2 activation is accompanied by enhanced H3K4me1, H3K27ac, and H3K14ac deposition on MT2. Zscan4c also interacts with GBAF chromatin remodelling complex through SCAN domain to further activate MT2 enhancer activity. Taken together, we delineate a previously unrecognized regulatory axis that Zscan4c interacts with and activates MT2/MERVL loci and their nearby genes through epigenetic regulation.

The role of human endogenous retroviruses in melanoma

2009 ◽  
Vol 161 (6) ◽  
pp. 1225-1231 ◽  
Author(s):  
S. Singh ◽  
S. Kaye ◽  
M.E. Gore ◽  
M.O. McClure ◽  
C.B. Bunker
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses

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

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3751-3751 ◽  
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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