USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA


Autoři: Hong-Yan Zhang aff001;  Bo-Wei Liao aff001;  Zhi-Sheng Xu aff001;  Yong Ran aff001;  Dong-Peng Wang aff001;  Yan Yang aff001;  Wei-Wei Luo aff001;  Yan-Yi Wang aff001
Působiště autorů: Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China aff001;  University of Chinese Academy of Sciences, Beijing, China aff002
Vyšlo v časopise: USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008178
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008178

Souhrn

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.

Klíčová slova:

DNA transcription – DNA viruses – Enzyme regulation – Immune response – Immunoblotting – Interferons – Plasmid construction – Vector-borne diseases


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