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Human Herpesvirus 6B Induces Hypomethylation on Chromosome 17p13.3, Correlating with Increased Gene Expression and Virus Integration

Authors :
Albert J. Becker
Anna Fogdell-Hahn
Pitt Niehusmann
Sarah Wideman
Tomas J. Ekström
Malin Almgren
Elin Engdahl
Nicky Dunn
Peter Wipfler
Source :
Journal of Virology. 91
Publication Year :
2017
Publisher :
American Society for Microbiology, 2017.

Abstract

Human herpesvirus 6B (HHV-6B) is a neurotropic betaherpesvirus that achieves latency by integrating its genome into host cell chromosomes. Several viruses can induce epigenetic modifications in their host cells, but no study has investigated the epigenetic modifications induced by HHV-6B. This study analyzed methylation with an Illumina 450K array, comparing HHV-6B-infected and uninfected Molt-3 T cells 3 days postinfection. Bisulfite pyrosequencing was used to validate the Illumina results and to investigate methylation over time in vitro . Expression of genes was investigated using quantitative PCR (qPCR), and virus integration was investigated with PCR. A total of 406 CpG sites showed a significant HHV-6B-induced change in methylation in vitro . Remarkably, 86% (351/406) of these CpGs were located IMPORTANCE The ability to establish latency in the host is a hallmark of herpesviruses, but the mechanisms differ. Human herpesvirus 6B (HHV-6B) is known to establish latency through integration of its genome into the telomeric regions of host cells, with the ability to reactivate. Our study is the first to show that HHV-6B specifically induces hypomethylated regions close to the telomeres and that integrating viruses may use the host methylation machinery to facilitate their integration process. The results from this study contribute to knowledge of HHV-6B biology and virus-host interaction. This in turn will lead to further progress in our understanding of the underlying mechanisms by which HHV-6B contributes to pathological processes and may have important implications in both disease prevention and treatment.

Details

ISSN :
10985514 and 0022538X
Volume :
91
Database :
OpenAIRE
Journal :
Journal of Virology
Accession number :
edsair.doi.dedup.....d2f9aeebd1cc1feed8a538ffc12ee4ec
Full Text :
https://doi.org/10.1128/jvi.02105-16