Better late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses

Dremel, Sarah E; Didychuk, Allison L.

doi:10.1016/j.semcdb.2022.12.001

Cited by 10 publications

(11 citation statements)

References 121 publications

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“…KSHV genes whose expression initiates prior to viral DNA replication (termed early genes) have promoters thought to assemble preinitiation complexes similar to host promoters. 58 Genes whose expression only initiates after the onset of viral DNA replication (termed late genes) have minimalistic promoters that require a complex of viral transcriptional activators, which functionally replace at least one and possibly multiple GTFs. [58][59][60] The observation that KSHV-induced stabilization of TFIIB requires early viral gene expression but not DNA replication or late gene expression is congruent with a role for TFIIB in early gene transcription.…”

Section: Tfiib Plays Key Roles During Viral Infectionmentioning

confidence: 99%

The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection

Gulyas,

Glaunsinger

2024

Preprint

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Many stressors, including viral infection, induce a widespread suppression of cellular RNA polymerase II (RNAPII) transcription, yet the mechanisms underlying transcriptional repression are not well understood. Here we find that a crucial component of the RNA polymerase II holoenzyme, general transcription factor IIB (TFIIB), is targeted for post-translational turnover by two pathways, each of which contribute to its depletion during stress. Upon DNA damage, translational stress, apoptosis, or lytic infection with the oncogenic Kaposi’s sarcoma-associated herpesvirus (KSHV), TFIIB is cleaved by activated caspase-3, leading to preferential downregulation of pro-survival genes. TFIIB is further targeted for rapid proteasome-mediated turnover by the E3 ubiquitin ligase TRIM28. KSHV counteracts proteasome-mediated turnover of TFIIB, thereby preserving a sufficient pool of TFIIB for transcription of viral genes. Thus, TFIIB may be a lynchpin for transcriptional outcomes during stress and a key target for nuclear replicating DNA viruses that rely on host transcriptional machinery.Graphical Abstract

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Section: Tfiib Plays Key Roles During Viral Infectionmentioning

confidence: 99%

The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection

Gulyas,

Glaunsinger

2024

Preprint

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“…IE gene products stimulate the expression of E and L genes or regulate the host to initiate virus replication. Many E genes are involved in DNA replication and many L genes create proteins required for virus assembly and egress ( 53 – 55 ). The previously discussed genes, Rta and ZEBRA, are classified as EBV immediate early genes (IE); they allow for the duplication of the genome, activation of later gene products in the EBV life cycle, and transactivation ( 56 , 57 ).…”

Section: Overview Of Infectionmentioning

confidence: 99%

“…BNLF2a is another E gene implicated in immune evasion through inhibition of peptide transporter associated with antigen processing (TAP) ( 61 ). Expression of late genes requires completion of viral genome replication ( 53 ). BcLF1 and BLLF1 are both late genes; BLLF1 encodes the glycoproteins 350 and 220 ( 62 ), while BcLF1 encodes the major capsid antigen ( 63 ).…”

Section: Overview Of Infectionmentioning

confidence: 99%

Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival

Sausen,

Poirier,

Spiers

et al. 2023

Front. Immunol.

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Epstein-Barr virus (EBV) is a prevalent oncogenic virus estimated to infect greater than 90% of the world’s population. Following initial infection, it establishes latency in host B cells. EBV has developed a multitude of techniques to avoid detection by the host immune system and establish lifelong infection. T cells, as important contributors to cell-mediated immunity, make an attractive target for these immunoevasive strategies. Indeed, EBV has evolved numerous mechanisms to modulate T cell responses. For example, it can augment expression of programmed cell death ligand-1 (PD-L1), which inhibits T cell function, and downregulates the interferon response, which has a strong impact on T cell regulation. It also modulates interleukin secretion and can influence major histocompatibility complex (MHC) expression and presentation. In addition to facilitating persistent EBV infection, these immunoregulatory mechanisms have significant implications for evasion of the immune response by tumor cells. This review dissects the mechanisms through which EBV avoids detection by host T cells and discusses how these mechanisms play into tumor survival. It concludes with an overview of cancer treatments targeting T cells in the setting of EBV-associated malignancy.

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“…In contrast, for the β-and γ-herpesviruses like cytomegalovirus (CMV) and Kaposi's sarcoma-associated herpesvirus (KSHV), late genes have strikingly minimal promoters, consisting only of a TATT sequence followed by a short degenerate motif in lieu of a canonical TATA box [2,3]. Late gene transcription additionally requires a dedicated set of six essential viral transcriptional activator (vTA) proteins that form a complex at late gene promoters [4][5][6][7][8][9][10]. In KSHV, the vTAs are encoded by ORF18, ORF24, ORF30, ORF31, ORF34, and ORF66.…”

Section: Introductionmentioning

confidence: 99%

The viral packaging motor potentiates Kaposi’s sarcoma-associated herpesvirus gene expression late in infection

et al. 2023

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β- and γ-herpesviruses transcribe their late genes in a manner distinct from host transcription. This process is directed by a complex of viral transcriptional activator proteins that hijack cellular RNA polymerase II and an unknown set of additional factors. We employed proximity labeling coupled with mass spectrometry, followed by CRISPR and siRNA screening to identify proteins functionally associated with the Kaposi’s sarcoma-associated herpesvirus (KSHV) late gene transcriptional complex. These data revealed that the catalytic subunit of the viral DNA packaging motor, ORF29, is both dynamically associated with the viral transcriptional activator complex and potentiates late gene expression. Through genetic mutation and deletion of ORF29, we establish that its catalytic activity potentiates viral transcription and is required for robust accumulation of essential late proteins during infection. Thus, we propose an expanded role for ORF29 that encompasses its established function in viral packaging and its newly discovered contributions to viral transcription and late gene expression in KSHV.

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Better late than never: A unique strategy for late gene transcription in the beta- and gammaherpesviruses

Cited by 10 publications

References 121 publications

The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection

The general transcription factor TFIIB is a target for transcriptome control during cellular stress and viral infection

Mechanisms of T cell evasion by Epstein-Barr virus and implications for tumor survival

The viral packaging motor potentiates Kaposi’s sarcoma-associated herpesvirus gene expression late in infection

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