2. Academic Validation
  3. The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection

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

  • Viruses. 2017 Nov 16;9(11):342. doi: 10.3390/v9110342.
Ben J Trigg 1,  Katharina B Lauer 2,  Paula Fernandes Dos Santos 3,  Heather Coleman 4,  Gabriel Balmus 5 6,  Daniel S Mansur 7,  Brian J Ferguson 8
Affiliations

Affiliations

  • 1 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. bjt40@cam.ac.uk.
  • 2 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. kbl23@cam.ac.uk.
  • 3 Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil. fernandes.santos.paula@gmail.com.
  • 4 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. hmc@mole.bio.cam.ac.uk.
  • 5 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK. gb318@cam.ac.uk.
  • 6 Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK. gb318@cam.ac.uk.
  • 7 Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil. daniel.mansur@ufsc.br.
  • 8 Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. bf234@cam.ac.uk.
PMID: 29144403 DOI: 10.3390/v9110342
Abstract

Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to be required for efficient replication of the viral genome, while different members of the classical non-homologous end-joining (c-NHEJ) pathway have opposing effects on HSV-1 Infection. Here, we have investigated the role of the recently-discovered c-NHEJ component, PAXX (Paralogue of XRCC4 and XLF), which we found to be excluded from the nucleus during HSV-1 Infection. We have established that cells lacking PAXX have an intact innate immune response to HSV-1 but show a defect in viral genome replication efficiency. Counterintuitively, PAXX-/- cells were able to produce greater numbers of infectious virions, indicating that PAXX acts to restrict HSV-1 Infection in a manner that is different from other c-NHEJ factors.

Keywords

DDR; DNA damage response; HSV-1; PAXX; c-NHEJ; classical non-homologous end joining; herpes simplex virus 1.

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