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

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.

Functions of DNA damage machinery in the innate immune response to DNA virus infection.

DNA is potently immunostimulatory, and self-DNA is packaged in the nucleus or mitochondria allowing it to remain silent to cell-intrinsic sensors. However, damaged or mislocalised self-DNA is sensed by our innate immune systems, resulting in the production of type I interferons (IFNI), chemokines and inflammatory cytokines. During DNA virus infection the detection of viral DNA genomes by pattern recognition receptors (PRRs) is essential for the initiation of IFNI responses and host defence against these pathogens.

The air-water interface determines the outcome of seeding during amyloidogenesis.

Amyloid formation is a hallmark of protein misfolding diseases (e.g. Type II diabetes mellitus).