title: Dissecting innate immune signaling in viral evasion of cytokine production.
abstract: In response to a viral infection, the host innate immune response is activated to up-regulate gene expression and production of antiviral cytokines. Conversely, viruses have evolved intricate strategies to evade and exploit host immune signaling for survival and propagation. Viral immune evasion, entailing host defense and viral evasion, provides one of the most fascinating and dynamic interfaces to discern the host-virus interaction. These studies advance our understanding in innate immune regulation and pave our way to develop novel antiviral therapies. Murine γHV68 is a natural pathogen of murine rodents. γHV68 infection of mice provides a tractable small animal model to examine the antiviral response to human KSHV and EBV of which perturbation of in vivo virus-host interactions is not applicable. Here we describe a protocol to determine the antiviral cytokine production. This protocol can be adapted to other viruses and signaling pathways. Recently, we have discovered that γHV68 hijacks MAVS and IKKβ, key innate immune signaling components downstream of the cytosolic RIG-I and MDA5, to abrogate NFΚB activation and antiviral cytokine production. Specifically, γHV68 infection activates IKKβ and that activated IKKβ phosphorylates RelA to accelerate RelA degradation. As such, γHV68 efficiently uncouples NFΚB activation from its upstream activated IKKβ, negating antiviral cytokine gene expression. This study elucidates an intricate strategy whereby the upstream innate immune activation is intercepted by a viral pathogen to nullify the immediate downstream transcriptional activation and evade antiviral cytokine production.
authors.affiliation: Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California.
authors.forename: Junjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California.
authors.forename: Lining
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Microbiology and Immunology, Keck School of Medicine, University of Southern California; pinghuif@usc.edu.
authors.forename: Pinghui
authors.initials: P
authors.lastname: Feng
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D018144:Rhadinovirus / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*
chemical_list: D016207:Cytokines