The bovine herpesvirus 1 regulatory proteins, bICP4 and bICP22, are expressed during the escape from latency

Guo, Junqing; Li, Qingmei; Jones, Clinton

doi:10.1007/s13365-018-0684-7

Cited by 14 publications

(8 citation statements)

References 49 publications

(54 reference statements)

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“…IE gene expression is activated by a virion component, VP16 (α-TIF), in cooperation with cellular transcription factors [9]. IE proteins bICP4 and bICP0 control the transcription of E genes, which encode enzymes needed for the synthesis of viral DNA [10]. The us1 gene has also been described as a transcription regulator [11,12].…”

Section: Introductionmentioning

confidence: 99%

In-Depth Temporal Transcriptome Profiling of an Alphaherpesvirus Using Nanopore Sequencing

Tombácz

Kakuk

Torma

et al. 2022

Viruses

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In this work, a long-read sequencing (LRS) technique based on the Oxford Nanopore Technology MinION platform was used for quantifying and kinetic characterization of the poly(A) fraction of bovine alphaherpesvirus type 1 (BoHV-1) lytic transcriptome across a 12-h infection period. Amplification-based LRS techniques frequently generate artefactual transcription reads and are biased towards the production of shorter amplicons. To avoid these undesired effects, we applied direct cDNA sequencing, an amplification-free technique. Here, we show that a single promoter can produce multiple transcription start sites whose distribution patterns differ among the viral genes but are similar in the same gene at different timepoints. Our investigations revealed that the circ gene is expressed with immediate–early (IE) kinetics by utilizing a special mechanism based on the use of the promoter of another IE gene (bicp4) for the transcriptional control. Furthermore, we detected an overlap between the initiation of DNA replication and the transcription from the bicp22 gene, which suggests an interaction between the two molecular machineries. This study developed a generally applicable LRS-based method for the time-course characterization of transcriptomes of any organism.

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Section: Introductionmentioning

confidence: 99%

In-Depth Temporal Transcriptome Profiling of an Alphaherpesvirus Using Nanopore Sequencing

Tombácz

Kakuk

Torma

et al. 2022

Viruses

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“…During the early stages of DEX-induced reactivation in TG, bICP0 and VP16 are detected before bICP4 and bICP22 [ 108 , 109 , 110 ]. Conversely, bICP4 mRNA, but not bICP0, bICP22, and VP16, is abundantly expressed within 30 min after DEX treatment in PT of latently infected calves [ 111 ].…”

Section: Lr Gene Products Modulate the Latency-reactivation Cyclementioning

confidence: 99%

The Bovine Herpesvirus 1 Latency-Reactivation Cycle, a Chronic Problem in the Cattle Industry

Ostler

Jones

2023

Viruses

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Bovine alphaherpesvirus 1 (BoHV-1) is a persistent and recurring disease that affects cattle worldwide. It is a major contributor to bovine respiratory disease and reproductive failure in the US. A major complication of BoHV-1 arises from the lifelong latent infection established in the sensory ganglia of the peripheral nervous system following acute infection. Lifelong latency is marked by periodic reactivation from latency that leads to virus transmission and transient immunosuppression. Physiological and environmental stress, along with hormone fluctuations, can drive virus reactivation from latency, allowing the virus to spread rapidly. This review discusses the mechanisms of the latency/reactivation cycle, with particular emphasis on how different hormones directly regulate BoHV-1 gene expression and productive infection. Glucocorticoids, including the synthetic corticosteroid dexamethasone, are major effectors of the stress response. Stress directly regulates BoHV-1 gene expression through multiple pathways, including β-catenin dependent Wnt signaling, and the glucocorticoid receptor. Related type 1 nuclear hormone receptors, the androgen and progesterone receptors, also drive BoHV-1 gene expression and productive infection. These receptors form feed-forward transcription loops with the stress-induced Krüppel-like transcription factors KLF4 and KLF15. Understanding these molecular pathways is critical for developing novel therapeutics designed to block reactivation and reduce virus spread and disease.

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“…In the context of a latent infection, BoHV-1 lytic cycle regulatory genes are not abundantly expressed during latency in calves, as judged by in situ hybridization studies (52) and immunohistochemistry studies (13)(14)(15). Thus, cellular transcription factors are predicted to trigger viral gene expression during the transition from latency to reactivation from latency.…”

Section: Figmentioning

confidence: 99%

“…For successful reactivation from latency to occur, the quiescent viral genome in latently infected neurons must be remodeled into an actively transcribing genome to produce infectious virus. BoHV-1 proteins encoded by all three immediate early (IE) genes (bICP0, bICP4, and bICP22) and the viral tegument protein that specifically activates IE promoters (VP16) are detected in TG neurons within hours after DEX treatment (13)(14)(15). Conversely, other late viral proteins (gC and gE, for example) are difficult to detect during reactivation.…”

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confidence: 99%

Two Pioneer Transcription Factors, Krüppel-Like Transcription Factor 4 and Glucocorticoid Receptor, Cooperatively Transactivate the Bovine Herpesvirus 1 ICP0 Early Promoter and Stimulate Productive Infection

El-mayet

Sawant

Thunuguntla

et al. 2020

J Virol

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An important site for bovine herpesvirus 1 (BoHV-1) latency is sensory neurons within trigeminal ganglia (TG). The synthetic corticosteroid dexamethasone consistently induces BoHV-1 reactivation from latency. Expression of four Krüppel-like transcription factors (KLF), i.e., KLF4, KLF6, PLZF (promyelocytic leukemia zinc finger), and KLF15, are induced in TG neurons early during dexamethasone-induced reactivation. The glucocorticoid receptor (GR) and KLF15 form a feed-forward transcription loop that cooperatively transactivates the BoHV-1 immediate early transcription unit 1 (IEtu1) promoter that drives bovine infected cell protein 0 (bICP0) and bICP4 expression. Since the bICP0 gene also contains a separate early (E) promoter, we tested the hypothesis that GR and KLF family members transactivate the bICP0 E promoter. GR and KLF4, both pioneer transcription factors, cooperated to stimulate bICP0 E promoter activity in a ligand-independent manner in mouse neuroblastoma cells (Neuro-2A). Furthermore, GR and KLF4 stimulated productive infection. Mutating both half GR binding sites did not significantly reduce GR- and KLF4-mediated transactivation of the bICP0 E promoter, suggesting that a novel mechanism exists for transactivation. GR and KLF15 cooperatively stimulated bICP0 activity less efficiently than GR and KL4: however, KLF6, PLZF, and GR had little effect on the bICP0 E promoter. GR, KLF4, and KLF15 occupied bICP0 E promoter sequences in transfected Neuro-2A cells. GR and KLF15, but not KLF4, occupied the bICP0 E promoter at late times during productive infection of bovine cells. Collectively, these studies suggest that cooperative transactivation of the bICP0 E promoter by two pioneer transcription factors (GR and KLF4) correlates with stimulating lytic cycle viral gene expression following stressful stimuli. IMPORTANCE Bovine herpesvirus 1 (BoHV-1), an important bovine pathogen, establishes lifelong latency in sensory neurons. Reactivation from latency is consistently induced by the synthetic corticosteroid dexamethasone. We predict that increased corticosteroid levels activate the glucocorticoid receptor (GR). Consequently, viral gene expression is stimulated by the activated GR. The immediate early transcription unit 1 promoter (IEtu1) drives expression of two viral transcriptional regulatory proteins, bovine infected cell protein 0 (bICP0) and bICP4. Interestingly, a separate early promoter also drives bICP0 expression. Two pioneer transcription factors, GR and Krüppel-like transcription factor 4 (KLF4), cooperatively transactivate the bICP0 early (E) promoter. GR and KLF15 cooperate to stimulate bICP0 E promoter activity but significantly less than GR and KLF4. The bICP0 E promoter contains enhancer-like domains necessary for GR- and KLF4-mediated transactivation that are distinct from those for GR and KLF15. Stress-induced pioneer transcription factors are proposed to activate key viral promoters, including the bICP0 E promoter, during early stages of reactivation from latency.

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The bovine herpesvirus 1 regulatory proteins, bICP4 and bICP22, are expressed during the escape from latency

Cited by 14 publications

References 49 publications

In-Depth Temporal Transcriptome Profiling of an Alphaherpesvirus Using Nanopore Sequencing

In-Depth Temporal Transcriptome Profiling of an Alphaherpesvirus Using Nanopore Sequencing

The Bovine Herpesvirus 1 Latency-Reactivation Cycle, a Chronic Problem in the Cattle Industry

Two Pioneer Transcription Factors, Krüppel-Like Transcription Factor 4 and Glucocorticoid Receptor, Cooperatively Transactivate the Bovine Herpesvirus 1 ICP0 Early Promoter and Stimulate Productive Infection

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