The Non-Homologous End Joining Protein PAXX Acts to Restrict HSV-1 Infection
Ben J. Trigg,
Katharina B. Lauer,
Paula Fernandes dos Santos,
Heather Coleman,
Gabriel Balmus,
Daniel S. Mansur,
Brian J. Ferguson
Affiliations
Ben J. Trigg
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
Katharina B. Lauer
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
Paula Fernandes dos Santos
Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil
Heather Coleman
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
Gabriel Balmus
Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge CB2 1QN, UK
Daniel S. Mansur
Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Santa Catarina 88040-900, Brazil
Brian J. Ferguson
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK
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.
