Modulation of Innate Immune Signaling Pathways by Herpesviruses.

Youliang Rao,Mao Tian,Qizhi Liu,Shu Zhang,Pinghui Feng

doi:10.3390/v11060572

Youliang Rao, Mao Tian + Show 3 more

Open Access

https://doi.org/10.3390/v11060572

Copy DOI

Journal: Viruses	Publication Date: Jun 21, 2019
Citations: 24	License type: CC BY 4.0

Affiliation: University of Southern California

Abstract

Herpesviruses can be detected by pattern recognition receptors (PRRs), which then activate downstream adaptors, kinases and transcription factors (TFs) to induce the expression of interferons (IFNs) and inflammatory cytokines. IFNs further activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, inducing the expression of interferon-stimulated genes (ISGs). These signaling events constitute host innate immunity to defeat herpesvirus infection and replication. A hallmark of all herpesviruses is their ability to establish persistent infection in the presence of active immune response. To achieve this, herpesviruses have evolved multiple strategies to suppress or exploit host innate immune signaling pathways to facilitate their infection. This review summarizes the key host innate immune components and their regulation by herpesviruses during infection. Also we highlight unanswered questions and research gaps for future perspectives.

Highlights

The innate immune response serves as the first line of defense against viral infections
A prototype member of the RIG-I-like receptor (RLR) family, RIG-I consists of two N-terminal caspase recruitment domains (CARDs), a central DEAD box helicase/ATPase domain and a
Roy et al found that Interferon Gamma Inducible Protein 16 (IFI16) is polyubiquitinated and degraded in a proteasome-dependent manner in tissue plasminogen activator (TPA)- or doxycycline-induced cells expressing lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) proteins [78], suggesting that KSHV gene products degrade IFI16 upon lytic reactivation

Summary

Introduction

The innate immune response serves as the first line of defense against viral infections. The exception is cyclic GMP-AMP synthase (cGAS) that catalyzes the synthesis of cyclic GMP–AMP (cGAMP), which in turn serves as a second messenger to activate the endoplasmic reticulum (ER)-anchored stimulator of interferon genes (STING) These two activated kinases promote nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor (IRF) activation, leading to the up-regulated expression and subsequent production of inflammatory cytokines such as IFNs. When bound to IFN receptors, IFNs further activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, inducing the expression of hundreds of genes, known as IFN-stimulated genes (ISGs), to establish an antiviral state [1]. Multiple steps in cytosolic PRR-mediated innate immune signaling pathways are inhibited or genes (ISGs). Multiple steps in cytosolic PRR-mediated innate immune signaling pathways are hijacked by herpesviruses. Ended symbols and arrows indicate the inhibition and hijacking by herpesvirus proteins, respectively

Cytosolic Sensors and Adaptors

RIG-I-MAVS

Other Herpesvirus Sensors

Immune Kinases and Transcscription Factors

IKKβ-NF-κB

TBK1-IRF3

ISGs with Direct Antiviral Activities

Viperin

Tetherin

JAK-STAT Pathway

Future Perspectives