Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation

Cliffe, Anna R.; Wilson, Angus C.

doi:10.1128/jvi.01419-16

Cited by 67 publications

(79 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two discrete waves of viral productive cycle gene transcription, termed Phases I and II, were identified in latently-infected cultured neurons following inducible reactivation (Kim et al, 2012). By phosphorylating histone H3 ser10 adjacent to repressive di- or trimethylated H3 lys9, the neuronal JNK stress pathway overrides epigenetic silencing to activate viral promoters in Phase I ( Cliffe et al, 2015 ; Cliffe & Wilson, 2016). The resulting burst of transcription from viral genomes includes all HSV-1 genes irrespective of their kinetic class [ immediate-early (IE), early, leaky-late and true-late ], is independent of protein or DNA synthesis, and proceeds without infectious virus production.…”

Section: Introductionmentioning

confidence: 99%

Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen

et al. 2017

Self Cite

View full text Add to dashboard Cite

SUMMARY How type I/II interferons prevent periodic reemergence of latent pathogens in tissues of diverse cell-types remains unknown. Using homogenous neuron cultures latently-infected with herpes simplex virus-1, we show that extrinsic type I or II interferon act directly on neurons to induce unique gene expression signatures and inhibit the reactivation-specific burst of viral genome-wide transcription called Phase I. Surprisingly, interferons suppressed reactivation only during a limited period early in Phase I preceding productive virus growth. Sensitivity to type II interferon was selectively lost if viral ICP0, which normally accumulates later in Phase I, was expressed before reactivation. Thus, interferons suppress reactivation by preventing initial expression of latent genomes but are ineffective once Phase I viral proteins accumulate, limiting interferon action. This demonstrates that inducible reactivation from latency is only transiently sensitive to interferon. Moreover, it illustrates how latent pathogens escape host immune control to periodically replicate by rapidly deploying an interferon-resistant state.

show abstract

Section: Introductionmentioning

confidence: 99%

Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…These findings presented here could be of general interest as the expression of HSV TK in cancer cells has been recently exploited in strategies for cancer therapy [64]. Moreover, the reactivation of silent HSV copies in nerve cells is a common occurring health risk and the expression of HSV TK is crucial for the reactivation of HSV in human nervous cells [65].…”

mentioning

confidence: 71%

Optimizing fluorescent protein expression for quantitative fluorescence microscopy and spectroscopy using herpes simplex thymidine kinase promoter sequences

et al. 2018

View full text Add to dashboard Cite

The modulation of expression levels of fluorescent fusion proteins ( FFP s) is central for recombinant DNA technologies in modern biology as overexpression of proteins contributes to artifacts in biological experiments. In addition, some microscopy techniques such as fluorescence correlation spectroscopy ( FCS ) and single‐molecule‐based techniques are very sensitive to high expression levels of FFP s. To reduce the levels of recombinant protein expression in comparison with the commonly used, very strong CMV promoter, the herpes simplex virus thymidine kinase ( TK ) gene promoter, and mutants thereof were analyzed. Deletion mutants of the TK promoter were constructed and introduced into the Gateway ® system for ectopic expression of enhanced green fluorescent protein ( eGFP ), monomeric cherry ( mC herry), and FFP s containing these FP s. Two promoter constructs, TK 2 ST and TKTSC , were established, which have optimal low expression levels suitable for FCS studies in U2 OS , HeLa CCL 2, NIH 3T3, and BALB /c cells. Interestingly, when tested in these four cell lines, promoter constructs having a deletion within TK gene 5′‐ UTR showed significantly higher protein expression levels than the equivalent constructs lacking this deletion. This suggests that a negative regulatory element is localized within the TK gene 5′‐UTR.

show abstract

“…As reviewed recently, the process of reactivation likely requires multiple steps (Cliffe and Wilson, 2017; Sawtell and Thompson, 2016a). In primary neuronal culture systems, it has been shown that there is an initial relaxing of the chromatin structure, which likely includes multiple changes that may or may not be accompanied by detectable increases in lytic gene transcription.…”

Section: Triggers Implicated In Hsv Reactivationmentioning

confidence: 99%

“…In this context, reactivation occurs as a two-stage program that overcomes a more compact viral chromatin structure and the absence of tegument factors, such as VP16 (reviewed in Cliffe and Wilson, 2017). During the first stage, termed phase I, there is a transient burst of lytic gene transcription.…”

Section: Loss Of Neurotrophin-associated Signalingmentioning

confidence: 99%

Strength in diversity: Understanding the pathways to herpes simplex virus reactivation

2018

Self Cite

View full text Add to dashboard Cite

Herpes simplex virus (HSV) establishes a latent infection in peripheral neurons and can periodically reactivate to cause disease. Reactivation can be triggered by a variety of stimuli that can activate different cellular processes to result in increased HSV lytic gene expression and production of infectious virus. The use of model systems has contributed significantly to our understanding of how reactivation of the virus is triggered by different physiological stimuli that are correlated with recrudescence of human disease. Furthermore, these models have led to the identification of both common and distinct mechanisms of different HSV reactivation pathways. Here, we summarize how the use of these diverse model systems has led to a better understanding of the complexities of HSV reactivation, and we present potential models linking cellular signaling pathways to changes in viral gene expression.

show abstract

Restarting Lytic Gene Transcription at the Onset of Herpes Simplex Virus Reactivation

Cited by 67 publications

References 39 publications

Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen

Immune Escape via a Transient Gene Expression Program Enables Productive Replication of a Latent Pathogen

Optimizing fluorescent protein expression for quantitative fluorescence microscopy and spectroscopy using herpes simplex thymidine kinase promoter sequences

Strength in diversity: Understanding the pathways to herpes simplex virus reactivation

Contact Info

Product

Resources

About