title: Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection.
abstract: Herpes simplex virus (HSV) persists in its human host and evades the immune response by undergoing a latent infection in sensory neurons, from which it can reactivate periodically. HSV expresses >80 gene products during productive ("lytic") infection, but only the latency-associated transcript (LAT) gene is expressed at abundant levels during latent infection. The LAT gene has been shown to repress lytic-gene expression in sensory neurons. In this study, we use chromatin immunoprecipitation to show that HSV lytic-gene promoters become complexed with modified histones associated with heterochromatin during the course of establishment of latent infection. Experiments comparing LAT-negative and LAT-positive viruses show that a function encoded by the LAT gene increases the amount of dimethyl lysine 9 form of histone H3 or heterochromatin and reduces the amount of dimethyl lysine 4 form of histone H3, a part of active chromatin, on viral lytic-gene promoters. Thus, HSV, and in particular the HSV LAT gene, may manipulate the cellular histone modification machinery to repress its lytic-gene expression and contribute to the persistence of its genome in a quiescent form in sensory neurons.
authors.affiliation: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Qing-Yin
authors.initials: QY
authors.lastname: Wang
authors.forename: Changhong
authors.initials: C
authors.lastname: Zhou
authors.forename: Karen E
authors.initials: KE
authors.lastname: Johnson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Colgrove
authors.forename: Donald M
authors.initials: DM
authors.lastname: Coen
authors.forename: David M
authors.initials: DM
authors.lastname: Knipe
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation; D015967:Gene Expression Regulation, Viral; D006561:Herpes Simplex / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000502:physiology*; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D035683:MicroRNAs; D011401:Promoter Regions, Genetic; D014764:Viral Proteins / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics*
chemical_list: D006570:Heterochromatin; D006657:Histones; D035683:MicroRNAs; D014764:Viral Proteins; C477253:latency associated transcript, herpes simplex virus-1