Herpesviral latency-associated transcript gene promotes assembly of heterochromatin on viral lytic-gene promoters in latent infection.
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.
Wang
Qing-Yin
QY
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Zhou
Changhong
C
Johnson
Karen E
KE
Colgrove
Robert C
RC
Coen
Donald M
DM
Knipe
David M
DM
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*
D006570:Heterochromatin; D006657:Histones; D035683:MicroRNAs; D014764:Viral Proteins; C477253:latency associated transcript, herpes simplex virus-1