An Essential Viral Transcription Activator Modulates Chromatin Dynamics

Gibeault, Rebecca; Conn, Kristen L.; Bildersheim, Michael D.; Schang, Luis M.

doi:10.1371/journal.ppat.1005842

Cited by 19 publications

(35 citation statements)

References 77 publications

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“…Maintenance of heterochromatin during chromatin stress, such as transcription and replication. Although viral chromatin structure is known to be dynamic (Gibeault et al, 2016), before this report, the formation of viral chromatin and the maintenance of viral chromatin were not understood to be separate mechanisms. Importantly, DNA viruses have evolved specific mechanisms for dismantling or disabling the ATRX/DAXX pathway rather than blocking the initial formation of heterochromatin.…”

Section: Discussionmentioning

confidence: 94%

ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

Cabral

Knipe

2018

eLife

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The mechanisms by which mammalian cells recognize and epigenetically restrict viral DNA are not well defined. We used herpes simplex virus with bioorthogonally labeled genomes to detect host factors recruited to viral DNA shortly after its nuclear entry and found that the cellular IFI16, PML, and ATRX proteins colocalized with viral DNA by 15 min post infection. HSV-1 infection of ATRX-depleted fibroblasts resulted in elevated viral mRNA and accelerated viral DNA accumulation. Despite the early association of ATRX with vDNA, we found that initial viral heterochromatin formation is ATRX-independent. However, viral heterochromatin stability required ATRX from 4 to 8 hr post infection. Inhibition of transcription blocked viral chromatin loss in ATRX-knockout cells; thus, ATRX is uniquely required for heterochromatin maintenance during chromatin stress. These results argue that the initial formation and the subsequent maintenance of viral heterochromatin are separable mechanisms, a concept that likely extrapolates to host cell chromatin and viral latency.

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Section: Discussionmentioning

confidence: 94%

ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

Cabral

Knipe

2018

eLife

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“…Viral immediate-early proteins may participate in this process. For example, the HSV ICP4 protein changes core histone dynamics in ways that may mobilize histones away from the viral genome [59] and HCMV IE2 counteracts the repressive effect of histone H1 [14]. In contrast, the host genome remains highly associated with histones organized in nucleosomes.…”

Section: Discussionmentioning

confidence: 99%

Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

Ball

Collins

et al. 2020

PLoS Pathog

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Herpesvirus late promoters activate gene expression after viral DNA synthesis has begun. Alphaherpesviruses utilize a viral immediate-early protein to do this, whereas beta-and gammaherpesviruses primarily use a 6-member set of viral late-acting transcription factors (LTF) that are drawn to a TATT sequence in the late promoter. The betaherpesvirus, human cytomegalovirus (HCMV), produces three immediate-early 2 protein isoforms, IE2-86, IE2-60, IE2-40, late in infection, but whether they activate late viral promoters is unknown. Here, we quickly degrade the IE2 proteins in late infection using dTag methodology and analyze effects on transcription using customized PRO-Seq and computational methods combined with multiple validation methods. We discover that the IE2 proteins selectively drive RNA Pol II transcription initiation at a subset of viral early-late and late promoters common to different HCMV strains, but do not substantially affect Pol II transcription of the 9,942 expressed host genes. Most of the IE2-activated viral late infection promoters lack the TATT sequence bound by the HCMV UL87-encoded LTF. The HCMV TATT-binding protein is not mechanistically involved in late RNA expression from the IE2-activated TATT-less UL83 (pp65) promoter, as it is for the TATT-containing UL82 (pp71) promoter. While antecedent viral DNA synthesis is necessary for transcription from the late infection viral promoters, continued viral DNA synthesis is unnecessary. We conclude that in late infection the IE2 proteins target a distinct subset of HCMV early-late and late promoters for transcription initiation by RNA Pol II. Commencement of viral DNA replication renders the HCMV genome late promoters susceptible to late-acting viral transcription factors. PLOS PATHOGENSPLOS Pathogens | https://doi.org/10.1371/journal.ppat.

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“…Herpes simplex virus (HSV), for example, is a dsDNA virus that probably replicates in the nucleus and is packaged in capsids as a linear molecule in the cytoplasm. During the HSV lytic cycle, the viral genome circularizes and nucleosomes form along its genome ( 79 ) in a highly dynamic way that is modulated by a viral transcription factor ( 80 ). The strong induction of all host histone core genes observed throughout the OtV5 life cycle strongly suggests that the OtV5 genome is chromatinized during replication of the viral genome and that viral replication continues throughout the dark cycle, when many photosynthesis-dependent host processes are shut down ( 81 ).…”

Section: Discussionmentioning

confidence: 99%

Prasinovirus Attack of Ostreococcus Is Furtive by Day but Savage by Night

Derelle

Yau

Moreau

et al. 2018

J Virol

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Prasinoviruses are large DNA viruses that infect diverse genera of green microalgae worldwide in aquatic ecosystems, but molecular knowledge of their life cycles is lacking. Several complete genomes of both these viruses and their marine algal hosts are now available and have been used to show the pervasive presence of these species in microbial metagenomes. We have analyzed the life cycle of Ostreococcus tauri virus 5 (OtV5), a lytic virus, using transcriptome sequencing (RNASeq) from 12 time points of healthy or infected Ostreococcus tauri cells over a day/ night cycle in culture. In the day, viral gene transcription remained low while host nitrogen metabolism gene transcription was initially strongly repressed for two successive time points before being induced for 8 h, but during the night, viral transcription increased steeply while host nitrogen metabolism genes were repressed and many host functions that are normally reduced in the dark appeared to be compensated either by genes expressed from the virus or by increased expression of a subset of 4.4% of the host's genes. Some host cells underwent lysis progressively during the night, but a larger proportion were lysed the following morning. Our data suggest that the life cycles of algal viruses mirror the diurnal rhythms of their hosts.IMPORTANCE Prasinoviruses are common in marine environments, and although several complete genomes of these viruses and their hosts have been characterized, little is known about their life cycles. Here we analyze in detail the transcriptional changes occurring over a 27-h-long experiment in a natural diurnal rhythm, in which the growth of host cells is to some extent synchronized, so that host DNA replication occurs late in the day or early in the night and cell division occurs during the night. Surprisingly, viral transcription remains quiescent over the daytime, when the most energy (from light) is available, but during the night viral transcription activates, accompanied by expression of a few host genes that are probably required by the virus. Although our experiment was accomplished in the lab, cyclical changes have been documented in host transcription in the ocean. Our observations may thus be relevant for eukaryotic phytoplankton in natural environments.

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An Essential Viral Transcription Activator Modulates Chromatin Dynamics

Cited by 19 publications

References 77 publications

ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress

Human cytomegalovirus IE2 drives transcription initiation from a select subset of late infection viral promoters by host RNA polymerase II

Prasinovirus Attack of Ostreococcus Is Furtive by Day but Savage by Night

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