The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection

Trigg, Benjamin; Lauer, Katharina B.; Santos, Paula Fernandes dos; Coleman, Heather M.; Balmus, Gabriel; Mansur, Daniel Santos; Ferguson, Brian J.

doi:10.3390/v9110342

Cited by 9 publications

(8 citation statements)

References 75 publications

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“…Therefore, we think that herpesviruses also need to block NHEJ in favor of HR in order to achieve the loss of recircularization of their genomes. It was demonstrated that the NHEJ protein PAXX acts as a restriction factor for HSV-1 replication [65]. PAXX interacts with Ku80 and gets relocated after HSV-1 infection, and depletion of PAXX has been shown to enhance HSV-1 replication [65].…”

Section: Dna Damage Response Proteinsmentioning

confidence: 99%

“…It was demonstrated that the NHEJ protein PAXX acts as a restriction factor for HSV-1 replication [65]. PAXX interacts with Ku80 and gets relocated after HSV-1 infection, and depletion of PAXX has been shown to enhance HSV-1 replication [65]. For KSHV, the depletion of Ku80 and DNA-PK, two proteins involved in NHEJ, leads to enhanced genome replication [56].…”

Section: Dna Damage Response Proteinsmentioning

confidence: 99%

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Early Nuclear Events after Herpesviral Infection

Full¹,

Ensser²

2019

JCM

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Herpesviruses are important pathogens that can cause significant morbidity and mortality in the human population. Herpesviruses have a double-stranded DNA genome, and viral genome replication takes place inside the nucleus. Upon entering the nucleus, herpesviruses have to overcome the obstacle of cellular proteins in order to enable viral gene expression and genome replication. In this review, we want to highlight cellular proteins that sense incoming viral genomes of the DNA-damage repair (DDR) pathway and of PML-nuclear bodies (PML-NBs) that all can act as antiviral restriction factors within the first hours after the viral genome is released into the nucleus. We show the function and significance of both nuclear DNA sensors, the DDR and PML-NBs, and demonstrate for three human herpesviruses of the alpha-, beta- and gamma-subfamilies, HSV-1, HCMV and KSHV respectively, how viral tegument proteins antagonize these pathways.

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Section: Dna Damage Response Proteinsmentioning

confidence: 99%

Section: Dna Damage Response Proteinsmentioning

confidence: 99%

Early Nuclear Events after Herpesviral Infection

Full¹,

Ensser²

2019

JCM

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“…Many components of the antiviral DDR pathways are degraded or inhibited by viral infection (reviewed in (Smith and Weller, 2015)). These include proteins involved in classic nonhomologous end joining (Lees-Miller et al, 1996;Parkinson et al, 1999;Trigg et al, 2017), homologous recombination signaling (Lilley et al, 2010), and ATR signaling involved in single strand DNA break repair (Mohni et al, 2010). Sensing of damaged DNA by the DDR system can detect the foreign DNA (especially open-ended DNA containing nicks and gaps) and may initiate a cascade of events to prevent viral gene expression before replication initiates (Lilley et al, 2011).…”

Section: Dna Damage Responsementioning

confidence: 99%

The Fate of Incoming HSV-1 Genomes Entering the Nucleus

Kobiler¹,

Afriat²

2021

Current Issues in Molecular Biology

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Herpesvirus genomes enter the eukaryotic nucleus as large linear double stranded DNA molecules that are free of any proteins (naked DNA). Once inside the nucleus, the HSV-1 genomes immediately associate with proteins that will be instrumental in the organization and regulation of these genomes.These initial interactions are thought to determine the fate of the infecting genomes. In general, the host cell has evolved several mechanisms to suppress viral genomes and induce latent or abortive infections. On the other hand, the virus has evolved to use viral and cellular factors to promote lytic infection. Recent findings suggest that not all viral genomes in the infected nucleus will develop progeny and that not all genetically identical cells will support successful virus propagation. Thus, the decision between different fates of infection is determined at both single-cell and single-genome levels.Here we summarize current knowledge on the conditions and interactions that lead to each outcome and discuss the unknown determinants.

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“…Co-immunoprecipitation experiments have shown that the interaction of Ku80 with Zta can be mapped to the region associated with DNA binding and dimerization, between amino acids 168 and 245 of Zta. [16], XRCC4 [17], Ku70 [20] Epstein Barr virus EBV Ku80 [24], DNA-PKcs [29] Herpes simplex virus 1 HSV-1 DNA-PKcs [10,34,37,39], Ku80 [38], Ku70 [39], Lig4/ XRCC4 [40], PAXX [42],…”

Section: Epstein Barr Virusmentioning

confidence: 99%

“…Although PAXX-knockout cells have an intact immune response, the virus seems to have a reproductive advantage and greater numbers of infectious virions are produced than in wild type cells. The authors suggest that PAXX acts to reduce the viral fitness by sequestering viral DNA in the cell leading to a reduced release of fully infectious HSV-1 particles [42].…”

Section: Introductionmentioning

confidence: 99%

Viral interactions with non-homologous end-joining: a game of hide-and-seek

Hristova

Lauer

Ferguson

2020

Journal of General Virology

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There are extensive interactions between viruses and the host DNA damage response (DDR) machinery. The outcome of these interactions includes not only direct effects on viral nucleic acids and genome replication, but also the activation of host stress response signalling pathways that can have further, indirect effects on viral life cycles. The non-homologous end-joining (NHEJ) pathway is responsible for the rapid and imprecise repair of DNA double-stranded breaks in the nucleus that would otherwise be highly toxic. Whilst directly repairing DNA, components of the NHEJ machinery, in particular the DNA-dependent protein kinase (DNA-PK), can activate a raft of downstream signalling events that activate antiviral, cell cycle checkpoint and apoptosis pathways. This combination of possible outcomes results in NHEJ being pro- or antiviral depending on the infection. In this review we will describe the broad range of interactions between NHEJ components and viruses and their consequences for both host and pathogen.

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The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection

Cited by 9 publications

References 75 publications

Early Nuclear Events after Herpesviral Infection

Early Nuclear Events after Herpesviral Infection

The Fate of Incoming HSV-1 Genomes Entering the Nucleus

Viral interactions with non-homologous end-joining: a game of hide-and-seek

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