scholarly journals Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis

2020 ◽  
Vol 6 (29) ◽  
pp. eabc0708 ◽  
Author(s):  
E. M. Johansson ◽  
D. Bouchet ◽  
R. Tamouza ◽  
P. Ellul ◽  
AS. Morr ◽  
...  
Keyword(s):  
Single Molecule ◽  
Cell Communication ◽  
Brain Cell ◽  
Endogenous Retroviruses ◽  
Synaptic Organization ◽  
Human Endogenous Retroviruses ◽  
Cell Functions ◽  
Synapse Maturation ◽  
Behavioral Impairments ◽  
Glutamate Synapse

Mobile genetic elements, such as human endogenous retroviruses (HERVs), produce proteins that regulate brain cell functions and synaptic transmission and have been implicated in the etiology of neurological and neurodevelopmental psychiatric disorders. However, the mechanisms by which these proteins of retroviral origin alter brain cell communication remain poorly understood. Here, we combined single-molecule tracking, calcium imaging, and behavioral approaches to demonstrate that the envelope protein (Env) of HERV type W, which is normally silenced but expressed in patients with neuropsychiatric conditions, alters the N-methyl-d-aspartate receptor (NMDAR)–mediated synaptic organization and plasticity through glia- and cytokine-dependent changes. Env expression in the developing hippocampus was sufficient to induce behavioral impairments at the adult stage that were prevented by Env neutralization or tuning of NMDAR trafficking. Thus, we show that a HERV gene product alters glutamate synapse maturation and generates behavioral deficits, further supporting the possible etiological interplay between genetic, immune, and synaptic factors in psychosis.

Expression of human endogenous retroviruses and associated transcripts in Hodgkin lymphoma cells

2020 ◽  
Author(s):  
K Engel ◽  
A Krüger ◽  
V Vandrey ◽  
J Schneider ◽  
I Volkmer ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Endogenous Retroviruses ◽  
Lymphoma Cells ◽  
Human Endogenous Retroviruses

Human endogenous retroviruses HERV-H, HERV-W and HERV-K in preeclampsia

2019 ◽  
Vol 71 (3) ◽  
Author(s):  
Massimiliano Bergallo ◽  
Pier-Angelo Tovo ◽  
Enrico Bertino ◽  
Valentina Daprà ◽  
Alice Pirra ◽  
...  
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses

scholarly journals COVID-19 in Children: Expressions of Type I/II/III Interferons, TRIM28, SETDB1, and Endogenous Retroviruses in Mild and Severe Cases

2021 ◽  
Vol 22 (14) ◽  
pp. 7481
Author(s):  
Pier-Angelo Tovo ◽  
Silvia Garazzino ◽  
Valentina Daprà ◽  
Giulia Pruccoli ◽  
Cristina Calvi ◽  
...  
Keyword(s):  
Viral Infections ◽  
Severe Disease ◽  
Endogenous Retroviruses ◽  
Type I ◽  
Human Endogenous Retroviruses ◽  
Moderate Disease ◽  
Amplification Assay ◽  
Positive Correlations ◽  
Inducible Genes ◽  
Inflammatory Syndrome

Children with the new coronavirus disease 2019 (COVID-19) have milder symptoms and a better prognosis than adult patients. Several investigations assessed type I, II, and III interferon (IFN) signatures in SARS-CoV-2 infected adults, however no data are available for pediatric patients. RIM28 and SETDB1 regulate the transcription of multiple genes involved in the immune response as well as of human endogenous retroviruses (HERVs). Exogenous viral infections can trigger the activation of HERVs, which in turn can induce inflammatory and immune reactions. Despite the potential cross-talks between SARS-CoV-2 infection and TRIM28, SETDB1, and HERVs, information on their expressions in COVID-19 patients is lacking. We assessed, through a PCR real time Taqman amplification assay, the transcription levels of six IFN-I stimulated genes, IFN-II and three of its sensitive genes, three IFN-lIIs, as well as of TRIM28, SETDB1, pol genes of HERV-H, -K, and -W families, and of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis-associated retrovirus (MRSV) in peripheral blood from COVID-19 children nd in control uninfected subjects. Higher expression levels of IFN-I and IFN-II inducible genes were observed in 36 COVID-19-infected children with mild or moderate disease as compared to uninfected controls, whereas their concentrations decreased in 17 children with severe disease and in 11 with multisystem inflammatory syndrome (MIS-C). Similar findings were found for the expression of TRIM-28, SETDB1, and every HERV gene. Positive correlations emerged between the transcriptional levels of type I and II IFNs, TRIM28, SETDB1, and HERVs in COVID-19 patients. IFN-III expressions were comparable in each group of subjects. This preserved induction of IFN-λs could contribute to the better control of the infection in children as compared to adults, in whom IFN-III deficiency has been reported. The upregulation of IFN-I, IFN-II, TRIM28, SETDB1, and HERVs in children with mild symptoms, their declines in severe cases or with MIS-C, and the positive correlations of their transcription in SARS-CoV-2-infected children suggest that they may play important roles in conditioning the evolution of the infection.

scholarly journals Human Endogenous Retrovirus Reactivation: Implications for Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1999
Author(s):  
Annacarmen Petrizzo ◽  
Concetta Ragone ◽  
Beatrice Cavalluzzo ◽  
Angela Mauriello ◽  
Carmen Manolio ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Genetic Material ◽  
Endogenous Retrovirus ◽  
Endogenous Retroviruses ◽  
Human Endogenous Retrovirus ◽  
Danger Signal ◽  
Human Endogenous Retroviruses ◽  
Double Stranded Rna ◽  
Specific Antigens ◽  
Viral Mimicry

Human endogenous retroviruses (HERVs) derive from ancestral exogenous retroviruses whose genetic material has been integrated in our germline DNA. Several lines of evidence indicate that cancer immunotherapy may benefit from HERV reactivation, which can be induced either by drugs or by cellular changes occurring in tumor cells. Indeed, several studies indicate that HERV proviral DNA can be transcribed either to double-stranded RNA (dsRNA) that is sensed as a “danger signal” by pattern recognition receptors (PRRs), leading to a viral mimicry state, or to mRNA that is translated into proteins that may contribute to the landscape of tumor-specific antigens (TSAs). Alternatively, HERV reactivation is associated with the expression of long noncoding RNAs (lncRNAs). In this review, we will highlight recent findings on HERV reactivation in cancer and its implications for cancer immunotherapy.

scholarly journals Utility of next-generation RNA-sequencing in identifying chimeric transcription involving human endogenous retroviruses

Apmis ◽  
2016 ◽  
Vol 124 (1-2) ◽  
pp. 127-139 ◽  
Author(s):  
Martin Sokol ◽  
Karen Margrethe Jessen ◽  
Finn Skou Pedersen
Keyword(s):  
Rna Sequencing ◽  
Endogenous Retroviruses ◽  
Next Generation ◽  
Human Endogenous Retroviruses

Regulation of human endogenous retroviruses of the W family by type III interferon λ2 and HIV in astrocytes

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 65
Author(s):  
Alessandra Mei ◽  
Giuseppe Mameli ◽  
Caterina Serra ◽  
Luciana Poddighe ◽  
Elena Uleriand ◽  
...  
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses ◽  
Type Iii ◽  
Type Iii Interferon

Brain-Protective Mechanisms of Transcription Factor NRF2: Toward a Common Strategy for Neurodegenerative Diseases

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Antonio Cuadrado
Keyword(s):  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Cell ◽  
Current Status ◽  
Annual Review ◽  
Publication Date ◽  
Related Factor ◽  
Protective Mechanisms ◽  
Cell Functions ◽  
Pass Through

Neurodegenerative diseases are characterized by the loss of homeostatic functions that control redox and energy metabolism, neuroinflammation, and proteostasis. The transcription factor nuclear factor erythroid 2–related factor 2 (NRF2) is a master controller of these functions, and its overall activity is compromised during aging and in these diseases. However, NRF2 can be activated pharmacologically and is now being considered a common therapeutic target. Many gaps still exist in our knowledge of the specific role that NRF2 plays in specialized brain cell functions or how these cells respond to the hallmarks of these diseases. This review discusses the relevance of NRF2 to several hallmark features of neurodegenerative diseases and the current status of pharmacological activators that might pass through the blood-brain barrier and provide a disease-modifying effect. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Aging-associated patterns in the expression of human endogenous retroviruses

PLoS ONE ◽  
2018 ◽  
Vol 13 (12) ◽  
pp. e0207407 ◽  
Author(s):  
Tapio Nevalainen ◽  
Arttu Autio ◽  
Binisha Hamal Mishra ◽  
Saara Marttila ◽  
Marja Jylhä ◽  
...  
Keyword(s):  
Endogenous Retroviruses ◽  
Human Endogenous Retroviruses

scholarly journals Minireview: The Neuroendocrine Regulation of Puberty: Is the Time Ripe for a Systems Biology Approach?

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1166-1174 ◽  
Author(s):  
Sergio R. Ojeda ◽  
Alejandro Lomniczi ◽  
Claudio Mastronardi ◽  
Sabine Heger ◽  
Christian Roth ◽  
...  
Keyword(s):  
Global Analysis ◽  
Single Gene ◽  
Functional Integration ◽  
Cell Communication ◽  
Cell Interaction ◽  
Specific Cell ◽  
Gnrh Secretion ◽  
Cell Functions ◽  
Hierarchical Arrangement ◽  
Cell Cell

The initiation of mammalian puberty requires an increase in pulsatile release of GnRH from the hypothalamus. This increase is brought about by coordinated changes in transsynaptic and glial-neuronal communication. As the neuronal and glial excitatory inputs to the GnRH neuronal network increase, the transsynaptic inhibitory tone decreases, leading to the pubertal activation of GnRH secretion. The excitatory neuronal systems most prevalently involved in this process use glutamate and the peptide kisspeptin for neurotransmission/neuromodulation, whereas the most important inhibitory inputs are provided by γ-aminobutyric acid (GABA)ergic and opiatergic neurons. Glial cells, on the other hand, facilitate GnRH secretion via growth factor-dependent cell-cell signaling. Coordination of this regulatory neuronal-glial network may require a hierarchical arrangement. One level of coordination appears to be provided by a host of unrelated genes encoding proteins required for cell-cell communication. A second, but overlapping, level might be provided by a second tier of genes engaged in specific cell functions required for productive cell-cell interaction. A third and higher level of control involves the transcriptional regulation of these subordinate genes by a handful of upper echelon genes that, operating within the different neuronal and glial subsets required for the initiation of the pubertal process, sustain the functional integration of the network. The existence of functionally connected genes controlling the pubertal process is consistent with the concept that puberty is under genetic control and that the genetic underpinnings of both normal and deranged puberty are polygenic rather than specified by a single gene. The availability of improved high-throughput techniques and computational methods for global analysis of mRNAs and proteins will allow us to not only initiate the systematic identification of the different components of this neuroendocrine network but also to define their functional interactions.

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