%0 Journal Article
%T USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA
%A Bo-Wei Liao
%A Dong-Peng Wang
%A Hong-Yan Zhang
%A Wei-Wei Luo
%A Yan Yang
%A Yan-Yi Wang
%A Yong Ran
%A Zhi-Sheng Xu
%J -
%D 2020
%R 10.1371/journal.ppat.1008178
%X Mediator of IRF3 activation (MITA, also known as stimulator of interferon genes, STING) senses the second messenger cyclic GMP-AMP (cGAMP) which is synthesized upon DNA virus infection and activates innate antiviral immune response. It has been demonstrated that the activity of MITA is delicately regulated by various post-translational modifications including polyubiquitination. In this study, we identified the deubiquitinating enzyme USP44 as a positive regulator of MITA. USP44 is recruited to MITA following DNA virus infection and removes K48-linked polyubiquitin moieties from MITA at K236, therefore prevents MITA from proteasome mediated degradation. USP44-deficiency results in acceleration of HSV-1-induced degradation of MITA and reduced induction of type I interferons (IFNs) and proinflammatory cytokines. Consistently, Usp44-/- mice are more susceptible to HSV-1 infection as indicated by higher tissue viral titers, greater tissue damage and lower survival rate. These findings suggest that USP44 plays a specific and critical role in the regulation of innate immune response against DNA viruses
%K Immune response
%K DNA transcription
%K Plasmid construction
%K DNA viruses
%K Immunoblotting
%K Vector-borne diseases
%K Enzyme regulation
%K Interferons
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008178