Long non-coding and endogenous retroviral RNA levels are associated with proinflammatory cytokine mRNA expression in peripheral blood cells: Implications for schizophrenia

Melbourne, Jennifer K.; Chase, Kayla A.; Feiner, Benjamin; Rosen, Cherise; Sharma, Rajiv P.

doi:10.1016/j.psychres.2017.09.025

Cited by 17 publications

(11 citation statements)

References 19 publications

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“…Frank analyzed Syncytin-1 mRNA expression in the brain of seven healthy individuals and seven individuals with schizophrenia, no differences were found between the groups ( 23 ). Meanwhile, similar levels of Syncytin-1 expression were observed in the PBMCs of patients with schizophrenia and controls ( 24 , 25 ). The inconsistencies with previous findings may be attributable to the following: First, variation in sample size might have influenced the statistical conclusion.…”

Section: Syncytin-1 and Neurological Diseasessupporting

confidence: 55%

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

2018

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Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome. Recent studies have considered HERVs as potential pathogenic factors. The majority of HERV genes are mutated and not capable of encoding functional proteins; regardless, some HERV genes, such as HERV-W envelope (env) glycoprotein, are known to have intact open reading frames. The HERV-W element on 7q21.2, which encodes a protein referred to as Syncytin-1, participates in human placental morphogenesis and can activate a pro-inflammatory and autoimmune cascade. Neuropsychological disorders are typically linked to inflammatory abnormalities. In this study, we review that Syncytin-1 has been increasingly involved in the development of neuropsychological disorders, such as schizophrenia and multiple sclerosis (MS). This study also presents inflammation imbalances in schizophrenia and MS. More importantly, we discuss the potential role and molecular mechanisms by which Syncytin-1 regulates inflammatory abnormalities in neuropsychological diseases. In summary, Syncytin-1 activity may represent a novel molecular pathogenic mechanism in neuropyschological diseases, such as schizophrenia and MS.

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Section: Syncytin-1 and Neurological Diseasessupporting

confidence: 55%

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

2018

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“…This heterochromatin structure is also quite possibly assembled by lncRNAs, as suggested by Figure 1 [3]. Our previous studies on the lncRNAs TMEVPG1 and NRON in participants with schizophrenia show that lncRNAs are responsive to inflammatory stimuli in a monocyte cell line, and have a relationship with atypical antipsychotics and pro-inflammatory cytokines [10].…”

Section: Introductionmentioning

confidence: 85%

Long Non-Coding RNAs Associated with Heterochromatin Function in Immune Cells in Psychosis

Sudhalkar

Rosen

Melbourne

et al. 2018

ncRNA

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Psychosis is associated with chronic immune dysregulation. Many long non-coding RNAs (lncRNAs) display abnormal expression during activation of immune responses, and play a role in heterochromatic regulation of gene promoters. We have measured lncRNAs MEG3, PINT and GAS5, selected for their previously described association with heterochromatin. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples collected from 86 participants with a diagnosis of psychosis and 44 control participants. Expression was assessed in relation to diagnosis, illness acuity status, and treatment with antipsychotic medication. We observed diagnostic differences with MEG3, PINT and GAS5, and symptom acuity effect with MEG3 and GAS5. Medication effects were evident in those currently on treatment with antipsychotics when compared to drug-naïve participants. We observed that clinical diagnosis and symptom acuity predict selected lncRNA expression. Particular noteworthy is the differential expression of MEG3 in drug naïve participants compared to those treated with risperidone. Additionally, an in vitro cell model using M2tol macrophages was used to test the effects of the antipsychotic drug risperidone on the expression of these lncRNAs using quantitative real-time PCR (qRT-PCR). Significant but differential effects of risperidone were observed in M2tol macrophages indicating a clear ability of antipsychotic medications to modify lncRNA expression.

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“…There is a considerable body of evidence demonstrating the presence of HERV-W/MSRV RNA and cDNA in samples taken from MS patients [ 52 , 68 , 71 , 78 , 181 ]. These findings are of importance given the presence of in vivo data demonstrating that HERV-W RNA can activate TLR3 on the endosomal membrane and melanoma differentiation–associated protein 5 (MDA5), protein kinase RNA-activated (PKR or eIF2AK2) and retinoic acid-inducible gene I (RIG-I) in the cytoplasm leading to the activation of NF-κB and the production of PICs and IRF3 and the production of type 1 interferons [ 182 – 184 ]. RIG-I and MDA5 are members of the RIG-I-like receptor (RLR) family, which recognise and activate in response to the presence of viral RNA in the cytoplasm.…”

Section: Potential Contribution Of Herv-w Herv-h and Herv-fc1 To Ms mentioning

confidence: 99%

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

et al. 2018

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The gammaretroviral human endogenous retrovirus (HERV) families MRSV/HERV-W and HERV-H (including the closely related HERV-Fc1) are associated with an increased risk of multiple sclerosis (MS). Complete HERV sequences betray their endogenous retroviral origin, with open reading frames in gag, pro, pol and env being flanked by two long terminal repeats containing promoter and enhancer sequences with the capacity to regulate HERV transactivation and the activity of host genes in spite of endogenous epigenetic repression mechanisms. HERV virions, RNA, cDNA, Gag and Env, and antibodies to HERV transcriptional products, have variously been found in the blood and/or brain and/or cerebrospinal fluid of MS patients, with the HERV expression level being associated with disease status. Furthermore, some HERV-associated single nucleotide polymorphisms (SNPs), such as rs662139 T/C in a 3-kb region of Xq22.3 containing a HERV-W env locus, and rs391745, upstream of the HERV-Fc1 locus on the X chromosome, are associated with MS susceptibility, while a negative association has been reported with SNPs in the tripartite motif-containing (TRIM) protein-encoding genes TRIM5 and TRIM22. Factors affecting HERV transcription include immune activation and inflammation, since HERV promoter regions possess binding sites for related transcription factors; oxidative stress, with oxidation of guanine to 8-oxoguanine and conversion of cytosine to 5-hydroxymethylcytosine preventing binding of methyl groups transferred by DNA methyltransferases; oxidative stress also inhibits the activity of deacetylases, thereby favouring the acetylation of histone lysine residues favouring gene expression; interferon beta; natalizumab treatment; impaired epigenetic regulation; and the sex of patients.

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Long non-coding and endogenous retroviral RNA levels are associated with proinflammatory cytokine mRNA expression in peripheral blood cells: Implications for schizophrenia

Cited by 17 publications

References 19 publications

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases

Long Non-Coding RNAs Associated with Heterochromatin Function in Immune Cells in Psychosis

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

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