Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies

Myoung, Jinjong; Lee, Shin-Ae; Lee, Hye‐Ra

doi:10.4014/jmb.1910.10004

Cited by 13 publications

(13 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A striking example for the exploitation of structural homology by viruses are the viral homologues of IRFs, termed vIRFs, which are encoded by some herpesviruses to interfere with the activity of host IRFs. For details on the interplay of vIRFs and host IRFs and their implications for the viral replication style, please refer to the recent review by Myoung and colleagues [ 219 ]. Shortly, vIRF1 of KSHV binds to IRF3 as well as p300 and in this way obstructs formation of the active holocomplex of IRF3 and CBP/p300 [ 220 , 221 , 222 ].…”

Section: Saboteurs Of the Main Act—viral Modulation Of Activated Imentioning

confidence: 99%

Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression

Schwanke

Stempel

Brinkmann

2020

Viruses

View full text Add to dashboard Cite

The type I interferon (IFN) response is a principal component of our immune system that allows to counter a viral attack immediately upon viral entry into host cells. Upon engagement of aberrantly localised nucleic acids, germline-encoded pattern recognition receptors convey their find via a signalling cascade to prompt kinase-mediated activation of a specific set of five transcription factors. Within the nucleus, the coordinated interaction of these dimeric transcription factors with coactivators and the basal RNA transcription machinery is required to access the gene encoding the type I IFN IFNβ (IFNB1). Virus-induced release of IFNβ then induces the antiviral state of the system and mediates further mechanisms for defence. Due to its key role during the induction of the initial IFN response, the activity of the transcription factor interferon regulatory factor 3 (IRF3) is tightly regulated by the host and fiercely targeted by viral proteins at all conceivable levels. In this review, we will revisit the steps enabling the trans-activating potential of IRF3 after its activation and the subsequent assembly of the multi-protein complex at the IFNβ enhancer that controls gene expression. Further, we will inspect the regulatory mechanisms of these steps imposed by the host cell and present the manifold strategies viruses have evolved to intervene with IFNβ transcription downstream of IRF3 activation in order to secure establishment of a productive infection.

show abstract

Section: Saboteurs Of the Main Act—viral Modulation Of Activated Imentioning

confidence: 99%

Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression

Schwanke

Stempel

Brinkmann

2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Innate immunity of the host is the first line of defense against viral infection [3,4]. RABV has been demonstrated to be recognized by innate immune sensors, such as retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated protein 5 (MDA5), and induces the production of type I IFN genes (IFN-α and IFN-β) in specific cells [5,6].…”

Section: Introductionmentioning

confidence: 99%

Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation

Zhao

Luo

et al. 2020

Viruses

View full text Add to dashboard Cite

Rabies, caused by rabies virus (RABV), is a fatal neurological disease that still causes more than 59,000 human deaths each year. Type III interferon IFN-λs are cytokines with type I IFN-like antiviral activities. Although IFN-λ can restrict the infection for some viruses, especially intestinal viruses, the inhibitory effect against RABV infection remains undefined. In this study, the function of type III IFN against RABV infection was investigated. Initially, we found that IFN-λ2 and IFN-λ3 could inhibit RABV replication in cells. To characterize the role of IFN-λ in RABV infection in a mouse model, recombinant RABVs expressing murine IFN-λ2 or IFN-λ3, termed as rB2c-IFNλ2 or rB2c-IFNλ3, respectively, were constructed and rescued. It was found that expression of IFN-λ could reduce the pathogenicity of RABV and limit viral spread in the brains by different infection routes. Furthermore, expression of IFN-λ could induce the activation of the JAK-STAT pathway, resulting in the production of interferon-stimulated genes (ISGs). It was also found that rRABVs expressing IFN-λ could reduce the production of inflammatory cytokines in primary astrocytes and microgila cells, restrict the opening of the blood-brain barrier (BBB), and prevent excessive infiltration of inflammatory cells into the brain, which could be responsible for the neuronal damage caused by RABV. Consistently, IFN-λ was found to maintain the integrity of tight junction (TJ) protein ZO-1 of BBB to alleviate neuroinflammation in a transwell model. Our study underscores the role of IFN-λ in inhibiting RABV infection, which potentiates IFN-λ as a possible therapeutic agent for the treatment of RABV infection.

show abstract

“…The innate immune system senses pathogens by recognizing pathogen-associated molecular patterns (PAMPs) such as melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I), which detect double-stranded (ds) RNAs in infected cells [5][6][7]. MDA5 and RIG-I, upon ligand binding, undergo conformational changes, mediating the activation of downstream signaling through CARD-CARD interactions [8][9][10][11]. Mitochondrial antiviral-signaling (MAVS) contains an N-terminal CARD that interacts with the CARDs of MDA5 and RIG-I, resulting in the activation of MAVS, which subsequently activates the downstream kinase proteins TBK1 and IKKε.…”

Section: Introductionmentioning

confidence: 99%

Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics

Bae

Lee

Myoung

2020

J. Microbiol. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Chikungunya virus (CHIKV) was first identified in 1952 as a causative agent of outbreaks. CHIKV is transmitted by two mosquito species, Aedes aegypti and A. albopictus . Symptoms after CHIKV infection in human are typically fever and joint pain, but can also include headache, muscle pain, joint swelling, polyarthralgia, and rash. CHIKV is an enveloped single-stranded, positive-sense RNA virus with a diameter of approximately 70 nm. The pathogenesis of CHIKV infection and the mechanism by which the virus evades the innate immune system remain poorly understood. Moreover, little is known about the roles of CHIKV-encoded genes in the viral evasion of host immune responses, especially type I interferon (IFN) responses. Therefore, in the present study, we screened CHIKV-encoded genes for their regulatory effect on the activation of nuclear factor kappa B (NF-κB), a critical transcription factor for the optimal activation of IFN-β. Among others, nonstructural protein 2 (nsP2) strongly inhibited melanoma differentiation-associated protein 5 (MDA5)-mediated induction of the NF-κB pathway in a dose-dependent manner. Elucidation of the detailed mechanisms of nsP2-mediated inhibition of the MDA5/RIG-I signaling pathway is anticipated to contribute to the development of virus-specific therapeutics against CHIKV infection.

show abstract

Beyond Viral Interferon Regulatory Factors: Immune Evasion Strategies

Cited by 13 publications

References 52 publications

Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression

Of Keeping and Tipping the Balance: Host Regulation and Viral Modulation of IRF3-Dependent IFNB1 Expression

Interferon-λ Attenuates Rabies Virus Infection by Inducing Interferon-Stimulated Genes and Alleviating Neurological Inflammation

Chikungunya Virus nsP2 Impairs MDA5/RIG-I-Mediated Induction of NF-κB Promoter Activation: A Potential Target for Virus-Specific Therapeutics

Contact Info

Product

Resources

About