title: Trimethylation of histone H3 lysine 4 by Set1 in the lytic infection of human herpes simplex virus 1.
abstract: Human herpes simplex virus 1 (HSV-1) is a double-stranded DNA virus that causes facial, ocular, and encephalitic disease in humans. Previous work showed that the genome of HSV-1 is associated with acetylated and methylated histones during lytic infection. However, the physiological role of histone modifications in lytic infection of HSV-1 is unclear. We examined the role of protein methylation in lytic infection of HSV-1 using a protein methylation inhibitor, 5'-deoxy-5'-methylthioadenosine (MTA). We found that MTA strongly reduces the transcription and replication of HSV-1. Moreover, MTA treatment decreases the level of trimethylation of lysine 4 in histone H3 (H3K4me3) on the HSV-1 genome. These results suggest that protein methylation, and in particular, histone methylation, is involved in the lytic infection of HSV-1. To delineate the underlying mechanism, we investigated the role of two H3K4 methyltransferases, Set1 and Set7/9, in the lytic infection of HSV-1. Using small interference RNA, we found that the reduction of Set1, but not Set7/9, reduces the transcription and replication of HSV-1 and specifically decreases H3K4me3 on the virus genome. These results indicate that H3K4me3 mediated by Set1 is required for optimal gene expression and replication of HSV-1 during lytic infection and suggest that this pathway could be a potential point of pharmacological intervention during HSV-1 infection.
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Kent
authors.forename: Brandon
authors.initials: B
authors.lastname: Placek
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Whelan
authors.forename: Charles M
authors.initials: CM
authors.lastname: Hollow
authors.forename: Ping-Yao
authors.initials: PY
authors.lastname: Zeng
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Fraser
authors.forename: Shelley L
authors.initials: SL
authors.lastname: Berger
mesh_terms: D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014779:Virus Replication
chemical_list: D006657:Histones; D008780:Methyltransferases; D008239:Lysine