Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity

Estekizadeh, Atosa; Karimi, Mohsen; Strååt, Klas; Ammerpohl, Ole; Zeitelhofer, Manuel; Jagodic, Maja; Mehrab-Mohseni, Marjan; Sjöholm, Louise K.; Rahbar, Afsar; Söderberg‐Nauclér, Cecilia; Ekström, Tomas J.

doi:10.4161/epi.20075

Cited by 36 publications

(30 citation statements)

References 45 publications

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“…Furthermore, HCMV alters epigenetic patterns in infected cells 56 and produces 26 viral encoded miRNAs that can affect cellular functions 57 . HCMV produces six anti-apoptotic proteins, two of which mediate resistance to chemotherapy 58,59 .…”

Section: Discussionmentioning

confidence: 99%

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Rahbar

Touma

Costa

et al. 2017

Clinical Breast Cancer

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MicroAbstractThe mechanisms involved in initiation and progression of breast cancer (BC), the most common malignancy and second leading cause of cancer deaths in women, are largely unknown. Human cytomegalovirus (HCMV) has been detected in primary BC, sentinel lymph nodes and brain metastases of BC patients. We found HCMV DNA, RNA, and proteins in BC, and their prevalence was higher in advanced cancer. HCMV levels correlated inversely with estrogen (P = 0.02) and progesterone (p = 0.003) receptor expression. HER2 expression was also found to

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Section: Discussionmentioning

confidence: 99%

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Rahbar

Touma

Costa

et al. 2017

Clinical Breast Cancer

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“…An increasing number of studies report changes in host genome CpG methylation following virus infection (27)(28)(29)(30). Interestingly, a recent report also suggests that mammalian GCM proteins are directly involved in active CpG demethylation (54).…”

Section: Discussionmentioning

confidence: 99%

“…An increasing body of literature suggests that viral infections can modify the methylation status of host DNA in cells of rat and human origin (27)(28)(29)(30). Recent publications suggest that influenza A virus can cause CpG demethylation by interfering with DNA methyltransferase (Dnmt) activity (31,32).…”

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confidence: 99%

Transcriptional Derepression of the ERVWE1 Locus following Influenza A Virus Infection

Nellåker

Sabunciyan

et al. 2014

J Virol

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Syncytin-1, a fusogenic protein encoded by a human endogenous retrovirus of the W family (HERV-W) element (ERVWE1), is expressed in the syncytiotrophoblast layer of the placenta. This locus is transcriptionally repressed in adult tissues through promoter CpG methylation and suppressive histone modifications. Whereas syncytin-1 appears to be crucial for the development and functioning of the human placenta, its ectopic expression has been associated with pathological conditions, such as multiple sclerosis and schizophrenia. We previously reported on the transactivation of HERV-W elements, including ERVWE1, during influenza A/WSN/33 virus infection in a range of human cell lines. Here we report the results of quantitative PCR analyses of transcripts encoding syncytin-1 in both cell lines and primary fibroblast cells. We observed that spliced ERVWE1 transcripts and those encoding the transcription factor glial cells missing 1 (GCM1), acting as an enhancer element upstream of ERVWE1, are prominently upregulated in response to influenza A/WSN/33 virus infection in nonplacental cells. Knockdown of GCM1 by small interfering RNA followed by infection suppressed the transactivation of ERVWE1. While the infection had no influence on CpG methylation in the ERVWE1 promoter, chromatin immunoprecipitation assays detected decreased H3K9 trimethylation (H3K9me3) and histone methyltransferase SETDB1 levels along with influenza virus proteins associated with ERVWE1 and other HERV-W loci in infected CCF-STTG1 cells. The present findings suggest that an exogenous influenza virus infection can transactivate ERVWE1 by increasing transcription of GCM1 and reducing H3K9me3 in this region and in other regions harboring HERV-W elements. IMPORTANCESyncytin-1, a protein encoded by the env gene in the HERV-W locus ERVWE1, appears to be crucial for the development and functioning of the human placenta and is transcriptionally repressed in nonplacental tissues. Nevertheless, its ectopic expression has been associated with pathological conditions, such as multiple sclerosis and schizophrenia. In the present paper, we report findings suggesting that an exogenous influenza A virus infection can transactivate ERVWE1 by increasing the transcription of GCM1 and reducing the repressive histone mark H3K9me3 in this region and in other regions harboring HERV-W elements. These observations have implications of potential relevance for viral pathogenesis and for conditions associated with the aberrant transcription of HERV-W loci.

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“…Aging [23], smoking [24,25], and heavy metal exposure [26,27], acrolein [28,29] have all been associated with changes in the DNA methylome, and with changes in DNMT expression, but the mechanisms by which these changes occur are largely unknown. DNA methyltransferases (DNMTs) such as DNMT1, DNMT3A and DNMT3B contribute to various physiologic and pathologic conditions including embryo implantation [30], cytomegalovirus infection [31], radiation [32], cancer, aging, neural cell differentiation [33]. In this study although DNMT3b was increased at 1 h, 2 h, and 4 h, and DNMT1 was not changed compared to control in acrolein 30 nm exposure.…”

Section: Discussionmentioning

confidence: 63%

Claudin 5 Transcripts Following Acrolein Exposure Affected by Epigenetic Enzyme

Moon¹,

Lee²,

Kim³

et al. 2015

J Clin Toxicol

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Background and objective: Acrolein is a highly reactive α, β-unsaturated aldehyde and a respiratory irritant that is ubiquitously present in the environment but that can also be generated endogenously at sites of inflammation. Apical junctional protein claudin 5 can be affected by acrolein. This study aimed to determine the impact of aberrant expression of DNMT1, DNMT3b, MBD3, and MeCP2 on acrolein induced claudin 5.

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Human cytomegalovirus infection is sensitive to the host cell DNA methylation state and alters global DNA methylation capacity

Cited by 36 publications

References 45 publications

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Low Expression of Estrogen Receptor-α and Progesterone Receptor in Human Breast Cancer Tissues Is Associated With High-Grade Human Cytomegalovirus Protein Expression

Transcriptional Derepression of the ERVWE1 Locus following Influenza A Virus Infection

Claudin 5 Transcripts Following Acrolein Exposure Affected by Epigenetic Enzyme

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