Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

<jats:title>ABSTRACT</jats:title><jats:p>Varicella-Zoster virus (VZV) causes chickenpox and shingles. Although infection is associated with severe morbidity in some individuals, the molecular mechanisms that determine innate immune responses remain poorly defined. We found that the cGAS/STING DNA sensing pathway was critically required for type I interferon (IFN) induction in response to VZV infection. Viral gene overexpression screening identified the essential VZV tegument protein ORF9 as a novel antagonist of DNA sensing via cGAS. Ectopically as well as virally expressed ORF9 bound to endogenous cGAS. Confocal microscopy revealed co-localisation of cGAS and ORF9, which blocked the type I IFN response to transfected DNA. ORF9 and cGAS also interacted directly in a cell-free system. Our data further suggest that ORF9 inhibited the production of cGAMP by cGAS. Taken together, our work highlights the importance of the cGAS/STING DNA sensing pathway for VZV recognition and identified an immune antagonist encoded by VZV that directly interferes with DNA sensing <jats:italic>via</jats:italic> cGAS.</jats:p>

Original publication

DOI

10.1101/2020.02.11.943415

Type

Journal article

Publisher

Cold Spring Harbor Laboratory

Publication Date

11/02/2020