Recent advances in understanding viral evasion of type I interferon

Taylor, Kathryne E.; Mossman, Karen

doi:10.1111/imm.12038

Cited by 134 publications

(112 citation statements)

References 100 publications

Supporting

Mentioning

110

Contrasting

Order By: Relevance

“…In order to favour their own replication, most viruses have evolved mechanisms to counteract the host's immune response (Feng et al, 2014b;Hoffmann et al, 2015;Taylor & Mossman, 2013). Previous studies have shown that enteroviruses such as the coxsackie B viruses (CVBs) block type I IFN production (Feng et al, 2014a;Mukherjee et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

Lind

Svedin

Domsgen

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

Type I IFNs play an important role in the immune response to enterovirus infections. Their importance is underscored by observations showing that many enteroviruses including coxsackie B viruses (CVBs) have developed strategies to block type I IFN production. Recent studies have highlighted a role for the type III IFNs (also called IFNls) in reducing permissiveness to infections with enteric viruses including coxsackievirus. However, whether or not CVBs have measures to evade the effects of type III IFNs remains unknown. By combining virus infection studies and different modes of administrating the dsRNA mimic poly I : C, we discovered that CVBs target both Toll-like receptor 3-and MDA5/RIG-I-mediated type III IFN expression. Consistent with this, the cellular protein expression levels of the signal transduction proteins TRIF and IPS1 were reduced and no hyperphosphorylation of interferon regulatory factor 3 was observed following infection with the virus. Notably, decreased expression of full-length TRIF and IPS1 and the appearance of cleavage products was observed upon both CVB3 infection and in cellular protein extracts incubated with recombinant 2A pro , indicating an important role for the viral protease in subverting the cellular immune system. Collectively, our study reveals that CVBs block the expression of type III IFNs, and that this is achieved by a similar mechanism as the virus uses to block type I IFN production. We also demonstrate that the virus blocks several intracellular viral recognition pathways of importance for both type I and III IFN production. The simultaneous targeting of numerous arms of the host immune response may be required for successful viral replication and dissemination.

show abstract

Section: Introductionmentioning

confidence: 99%

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

Lind

Svedin

Domsgen

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Studies have revealed that several viral proteins are not active until modified by cellular protein kinases (44). There are three primary functions of the modified viral proteins.…”

Section: Discussionmentioning

confidence: 99%

The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1

Wang

et al. 2016

J Virol

View full text Add to dashboard Cite

Spring viremia of carp virus (SVCV) is an efficient pathogen causing high mortality in the common carp. Fish interferon (IFN) is a powerful cytokine enabling host cells to establish an antiviral response; therefore, the strategies that SVCV uses to avoid the cellular IFN response were investigated. Here, we report that the SVCV P protein is phosphorylated by cellular TANK-binding kinase 1 (TBK1), which decreases IFN regulatory factor 3 (IRF3) phosphorylation and suppresses IFN production. First, overexpression of P protein inhibited the IFN promoter activation induced by SVCV and the IFN activity activated by the mitochondrial antiviral signaling protein (MAVS) although TBK1 activity was not blocked by P protein. Second, P protein colocalized and interacted with TBK1. Dominant negative experiments suggested that the TBK1 N-terminal kinase domain interacted with P protein and was essential for P protein and IRF3 phosphorylation. Finally, P protein overexpression reduced the IRF3 phosphorylation activated by TBK1 and reduced host cellular ifn transcription. Collectively, our data demonstrated that the SVCV P protein is a decoy substrate for the host phosphokinase TBK1, preventing IFN production and facilitating SVCV replication. IMPORTANCETBK1 is a pivotal phosphokinase that activates host IFN production to defend against viral infection; thus, it is a potential target for viruses to negatively regulate IFN response and facilitate viral evasion. We report that the SVCV P protein functions as a decoy substrate for cellular TBK1, leading to the reduction of IRF3 phosphorylation and suppression of IFN expression. These findings reveal a novel immune evasion mechanism of SVCV. In aquatic viruses, spring viremia of carp virus (SVCV) belongs to the genus Vesiculovirus of the family Rhabdoviridae and causes significant mortality in the common carp (Cyprinus carpio) (1). Regarding its genome structure, SVCV encodes an ϳ11-kb negative-sense, single-stranded RNA that encodes five proteins in the following order (3= to 5=): nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and viral RNA-dependent RNA polymerase (L) (2-4). The roles of these proteins in the replication and proliferation of rhabdovirus have been explored. N protein associates with viral RNA to form the nucleocapsid during viral assembly. M protein participates in the assembly and budding of virus, and G protein is involved in viral endocytosis. Moreover, as a phosphoprotein, the P protein is involved in several viral replication and assembly processes. As an example, the functional phosphorylated P protein interacts with the L protein to form a viral polymerase complex that interacts with the RNA template. In addition, the P protein also maintains the N protein in a soluble, encapsidation-competent form (1, 5).In host cells, viral RNAs can be recognized by the cellular immune system, triggering an antiviral response (6). In the cytoplasm, RIG-I-like receptors (RLRs), including RIG-I and MDA5, are the major pattern-recognition...

show abstract

“…It is well known that interferon binding to its receptor IFNAR could activate the Janus family protein kinases (JAKs) Tyk2 and Jak1, inducing site specific phosphorylation of tyrosine residues in the signal transducers and activator of transcription STAT1 and STAT2, leading to their activation and formation of a heterotrimeric complex containing IRF-9 (known as IFN-stimulated gene factor-3, ISGF3) (Taylor and Mossman, 2013). It has been found that each step of this interferon-mediated JAK/STAT signalling pathway is disrupted by herpes viral proteins (Figure 3).…”

Section: Phosphorylation-mediated Viral Regulation Of Isg Secretion Amentioning

confidence: 99%

“…PRR activation stimulates IκBα phosphorylation and degradation, releasing NF-κB to translocate to the nucleus and induce target genes (Taylor and Mossman, 2013). Inhibition of NF-κB is employed by viruses as an immune evasion strategy which is also closely linked to oncogenesis during gammaherpesvirus persistent infection.…”

Section: Phosphorylation-mediated Viral Inhibition Of Nf-κb and Inflamentioning

confidence: 99%

The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers

et al. 2017

View full text Add to dashboard Cite

Activation of specific sets of protein kinases by intracellular signal molecules has become more and more apparent in the past decade. Phosphorylation, one of key posttranslational modification events, is activated by kinase or regulatory protein and is vital for controlling many physiological functions of eukaryotic cells such as cell proliferation, differentiation, malignant transformation, and signal transduction mediated by external stimuli. Moreovers, the reversible modification of phosphorylation and dephosphorylation can result in different features of the target substrate molecules including DNA binding, protein-protein interaction, subcellular location and enzymatic activity, and is often hijacked by viral infection. Epstein-Barr virus (EBV) and Kaposi's sarcomaassociated herpesvirus (KSHV), two human oncogenic gamma-herpesviruses, are shown to tightly associate with many malignancies. In this review, we summarize the recent progresses on understanding of molecular properties and regulatory modes of cellular and viral proteins phosphorylation influenced by these two tumor viruses, and highlight the potential therapeutic targets and strategies against their related cancers.

show abstract

Recent advances in understanding viral evasion of type I interferon

Cited by 134 publications

References 100 publications

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

Coxsackievirus counters the host innate immune response by blocking type III interferon expression

The P Protein of Spring Viremia of Carp Virus Negatively Regulates the Fish Interferon Response by Inhibiting the Kinase Activity of TANK-Binding Kinase 1

The regulatory role of protein phosphorylation in human gammaherpesvirus associated cancers

Contact Info

Product

Resources

About