Herpesviruses and the Type III Interferon System

Yuan, Yin; Favoreel, Herman

doi:10.1007/s12250-020-00330-2

Cited by 19 publications

(14 citation statements)

References 82 publications

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“…For example, TLR2 recognizes HSV-1 protein gH/gL and gB, TLR3 recognizes dsRNA intermediates, and TLR9, IFI16 and cyclic GMP-AMP synthase (cGAS) recognize viral genomic DNA respectively (105)(106)(107). Downstream activities of PRR signaling lead to production of type 1 and possibly type III IFN (interferon lambda) expression, JAK-STAT mediated induction of the expression of IFNresponsive genes and expression of pro-inflammatory cytokines including interleukin 1b (IL-1b), tumor necrosis factor (TNF) and IL-12 (26,108). Uninfected cells in close vicinity of virus-infected cells are the main source of these cytokines.…”

Section: Innate Immunitymentioning

confidence: 99%

Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man

et al. 2021

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Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen. HSV-1 genomes persist in trigeminal ganglia neuronal nuclei as chromatinized episomes, while epithelial cells are typically killed by lytic infection. Fluctuations in anti-viral responses, broadly defined, may underlay periodic reactivations. The ganglionic immune response to HSV-1 infection includes cell-intrinsic responses in neurons, innate sensing by several cell types, and the infiltration and persistence of antigen-specific T-cells. The mechanisms specifying the contrasting fates of HSV-1 in neurons and epithelial cells may include differential genome silencing and chromatinization, dictated by variation in access of immune modulating viral tegument proteins to the cell body, and protection of neurons by autophagy. Innate responses have the capacity of recruiting additional immune cells and paracrine activity on parenchymal cells, for example via chemokines and type I interferons. In both mice and humans, HSV-1-specific CD8 and CD4 T-cells are recruited to ganglia, with mechanistic studies suggesting active roles in immune surveillance and control of reactivation. In this review we focus mainly on HSV-1 and the TG, comparing and contrasting where possible observational, interventional, and in vitro studies between humans and animal hosts.

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Section: Innate Immunitymentioning

confidence: 99%

Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man

et al. 2021

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“…Expression of the type III IFN receptors and production of type III IFN on the other hand are largely restricted to epithelial cells that line mucosal surfaces. This has led to the assumption that type III IFN can be considered a restricted first-line defense against viral pathogens that invade the body via mucosae of the intestinal, respiratory, and genital tracts, whereas type I IFN can trigger a more general, systemic antiviral response (8).…”

mentioning

confidence: 99%

Pseudorabies Virus Inhibits Type I and Type III Interferon-Induced Signaling via Proteasomal Degradation of Janus Kinases

Yuan

Romero

Favoreel

2021

J Virol

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Both type I and III interferons (IFNs) play a crucial role in host antiviral response by activating the JAK/STAT (Janus kinase/signal transducer and activator of transcription) signaling pathway to trigger the expression of antiviral IFN-stimulated genes (ISGs). We report that the porcine alphaherpesvirus pseudorabies virus (PRV) triggers proteasomal degradation of the key Janus kinases Jak1 and to a lesser exent Tyk2, thereby inhibiting both type I and III IFN-induced STAT1 phosphorylation and suppressing IFN-induced expression of ISGs. UV-inactivated PRV did not interfere with IFN signaling. In addition, deletion of the EP0 gene from the PRV genome or inhibition of viral genome replication did not affect PRV-induced inhibition of IFN signaling. To our knowledge, this is the first report describing Janus kinase degradation by alphaherpesviruses. These findings thus reveal a novel alphaherpesvirus evasion mechanism of type I and type III IFNs. IMPORTANCE Type I and III IFNs trigger signaling via Janus kinases that phosphorylate and activate STAT transcription factors, leading to the expression of antiviral interferon-stimulated genes (ISGs) that result in an antiviral state of host cells. Viruses have evolved various mechanisms to evade this response. Our results indicate that an alphaherpesvirus, the porcine pseudorabies virus (PRV), inhibits both type I and III IFNs signaling pathways by triggering proteasome-dependent degradation of the key Janus kinases Jak1 and Tyk2 and consequent inhibition of STAT1 phosphorylation and suppression of ISG expression. Moreover, we found that this inhibition is not caused by incoming virions and does not depend on expression of the viral EP0 protein or viral true late proteins. These data for the first time address alphaherpesvirus evasion of type III IFN-mediated signaling and reveal a previously uncharacterized alphaherpesvirus mechanism of IFN evasion via proteasomal degradation of Janus kinases.

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“…However, the exact mechanism by which it produces is not clearly explained. It has been claimed that the HSV molecular pattern is distinguished by TLR3 and TLR9 in the endosome as well as melanoma differentiation-associated gene 5 (MDA5) in the cytoplasm, which leads to the activation of nuclear factor κB (NF-κB), IRF3 and IRF7 transcription factors and their subsequent translocation to the nucleus, where they then stimulate IFN-λ gene transcription ( 52 ). In this process, the transcriptional mediator Med23 and anchoring protein repeat domain protein 1 (ANKRD1) target IRF7 and IRF3, individually, which promote the gene of type III IFN expression ( 53 , 54 ).…”

Section: Ifn Generation and Signals Transmissionmentioning

confidence: 99%

The gamble between oncolytic virus therapy and IFN

Tan

Wang

et al. 2022

Front. Immunol.

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Various studies are being conducted on oncolytic virotherapy which one of the mechanisms is mediating interferon (IFN) production by it exerts antitumor effects. The antiviral effect of IFN itself has a negative impact on the inhibition of oncolytic virus or tumor eradication. Therefore, it is very critical to understand the mechanism of IFN regulation by oncolytic viruses, and to define its mechanism is of great significance for improving the antitumor effect of oncolytic viruses. This review focuses on the regulatory mechanisms of IFNs by various oncolytic viruses and their combination therapies. In addition, the exerting and the producing pathways of IFNs are briefly summarized, and some current issues are put forward.

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Herpesviruses and the Type III Interferon System

Cited by 19 publications

References 82 publications

Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man

Local Immune Control of Latent Herpes Simplex Virus Type 1 in Ganglia of Mice and Man

Pseudorabies Virus Inhibits Type I and Type III Interferon-Induced Signaling via Proteasomal Degradation of Janus Kinases

The gamble between oncolytic virus therapy and IFN

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