The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection
by
Ben J. Trigg 1,†, Katharina B. Lauer 1,†, Paula Fernandes dos Santos 2, Heather Coleman 1, Gabriel Balmus 3,4
, Daniel S. Mansur 2 and Brian J. Ferguson 1,*
Ben J. Trigg 1,†, Katharina B. Lauer 1,†, Paula Fernandes dos Santos 2, Heather Coleman 1, Gabriel Balmus 3,4, Daniel S. Mansur 2 and Brian J. Ferguson 1,*
1
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
2
Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil
3
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
4
Wellcome Trust Sanger Institute, Cambridge CB10 1HH, UK
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Viruses 2017, 9(11), 342; https://doi.org/10.3390/v9110342
Received: 11 September 2017 / Revised: 2 November 2017 / Accepted: 6 November 2017 / Published: 16 November 2017
(This article belongs to the Special Issue Viruses and the DNA Damage Response)
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.
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Keywords:
herpes simplex virus 1; HSV-1; DNA damage response; DDR; PAXX; c-NHEJ; classical non-homologous end joining
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MDPI and ACS Style
Trigg, B.J.; Lauer, K.B.; Fernandes dos Santos, P.; Coleman, H.; Balmus, G.; Mansur, D.S.; Ferguson, B.J. The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection. Viruses 2017, 9, 342.
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