Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production | Academic Article individual record
abstract

Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2-/- mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS.

authors
author list (cited authors)
Ghosh, A., Shao, L., Sampath, P., Zhao, B., Patel, N. V., Zhu, J., ... Sarkar, S. N.
publication date
2019
publisher
Elsevier bv Publisher
published in
IMMUNITY Journal
keywords
  • Ifn
  • Rna Viruses
  • Mice
  • Rna Virus Infections
  • Cgamp
  • DNA Viruses
  • Interferon Type I
  • Signal Transduction
  • Cyclic AMP
  • Thp-1 Cells
  • Oasl
  • Mice, Inbred C57BL
  • Membrane Proteins
  • Animals
  • Cgas
  • DNA Virus Infections
  • Mice, Knockout
  • 2',5'-oligoadenylate Synthetase
  • RNA, Small Interfering
  • Transcriptional Signalling
  • DNA Virus
  • Humans
  • Virus Replication
  • Nucleotidyltransferases
altmetric score

18.8

citation count

12