tetano
Editor, Senior Moderator
J Virol. 2014 Jan 29. [Epub ahead of print]
Transcriptional de-repression of ERVWE1 following influenza A virus infection.
Li F, Nell?ker C, Sabunciyan S, Yolken RH, Jones-Brando L, Johansson AS, Owe-Larsson B, Karlsson H.
Author information
Abstract
Syncytin-1, a fusogenic protein encoded by a human endogenous retrovirus (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 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. We here report qPCR 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 up-regulated in response to influenza A/WSN/33 virus infection in non-placental cells. Knock-down of GCM1 by siRNA, 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 methytransferase SETDB1 levels along with viral 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.Importance Syncytin-1, a protein encoded by the env gene in the HERV-W locus ERVWE1 appears crucial for the development and functioning of the human placenta and is transcriptionally repressed in non-placental 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 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 aberrant transcription of HERV-W loci.
PMID:
24478419
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24478419
Transcriptional de-repression of ERVWE1 following influenza A virus infection.
Li F, Nell?ker C, Sabunciyan S, Yolken RH, Jones-Brando L, Johansson AS, Owe-Larsson B, Karlsson H.
Author information
Abstract
Syncytin-1, a fusogenic protein encoded by a human endogenous retrovirus (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 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. We here report qPCR 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 up-regulated in response to influenza A/WSN/33 virus infection in non-placental cells. Knock-down of GCM1 by siRNA, 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 methytransferase SETDB1 levels along with viral 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.Importance Syncytin-1, a protein encoded by the env gene in the HERV-W locus ERVWE1 appears crucial for the development and functioning of the human placenta and is transcriptionally repressed in non-placental 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 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 aberrant transcription of HERV-W loci.
PMID:
24478419
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24478419