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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Trigg, Ben J 
Lauer, Katharina B 
Fernandes Dos Santos, Paula 
Coleman, Heather 

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.

Description

Keywords

DDR, DNA damage response, HSV-1, PAXX, c-NHEJ, classical non-homologous end joining, herpes simplex virus 1, Animals, Cell Line, DNA End-Joining Repair, DNA-Binding Proteins, Genes, Viral, Genome, Viral, Herpes Simplex, Herpesvirus 1, Human, Humans, Interferons, Mice, Viral Proteins, Virion, Virus Replication

Journal Title

Viruses

Conference Name

Journal ISSN

1999-4915
1999-4915

Volume Title

9

Publisher

MDPI AG
Sponsorship
Wellcome Trust (201946/Z/16/Z)
Cancer Research UK (18796)