Dataset Information

Enterovirus 71 2C Protein Inhibits NF-?B Activation by Binding to RelA(p65).

ABSTRACT: Viruses evolve multiple ways to interfere with NF-?B signaling, a key regulator of innate and adaptive immunity. Enterovirus 71 (EV71) is one of primary pathogens that cause hand-foot-mouth disease. Here, we identify RelA(p65) as a novel binding partner for EV71 2C protein from yeast two-hybrid screen. By interaction with IPT domain of p65, 2C reduces the formation of heterodimer p65/p50, the predominant form of NF-?B. We also show that picornavirus 2C family proteins inhibit NF-?B activation and associate with p65 and IKK?. Our findings provide a novel mechanism how EV71 antagonizes innate immunity.

SUBMITTER: Du H

PROVIDER: S-EPMC4585786 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Enterovirus 71 2C Protein Inhibits NF-κB Activation by Binding to RelA(p65).

Du Haiwei H Yin Peiqi P Yang Xiaojie X Zhang Leiliang L Jin Qi Q Zhu Guofeng G

Scientific reports 20150923

Viruses evolve multiple ways to interfere with NF-κB signaling, a key regulator of innate and adaptive immunity. Enterovirus 71 (EV71) is one of primary pathogens that cause hand-foot-mouth disease. Here, we identify RelA(p65) as a novel binding partner for EV71 2C protein from yeast two-hybrid screen. By interaction with IPT domain of p65, 2C reduces the formation of heterodimer p65/p50, the predominant form of NF-κB. We also show that picornavirus 2C family proteins inhibit NF-κB activation an ...[more]

PMID: 26394554

Similar Datasets

Project description:The NF-κB signaling pathway is central to the innate and adaptive immune responses. Upon their detection of pathogen-associated molecular patterns, Toll-like receptors on the cell surface initiate signal transduction and activate the NF-κB pathway, leading to the production of a wide array of inflammatory cytokines, in attempt to eradicate the invaders. As a countermeasure, pathogens have evolved ways to subvert and manipulate this system to their advantage. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) are closely related bacteria responsible for major food-borne diseases worldwide. Via a needle-like protein complex called the type three secretion system (T3SS), these pathogens deliver virulence factors directly to host cells and modify cellular functions, including by suppressing the inflammatory response. Using gain- and loss-of-function screenings, we identified two bacterial effectors, NleC and NleE, that down-regulate the NF-κB signal upon being injected into a host cell via the T3SS. A recent report showed that NleE inhibits NF-κB activation, although an NleE-deficient pathogen was still immune-suppressive, indicating that other anti-inflammatory effectors are involved. In agreement, our present results showed that NleC was also required to inhibit inflammation. We found that NleC is a zinc protease that disrupts NF-κB activation by the direct cleavage of NF-κB's p65 subunit in the cytoplasm, thereby decreasing the available p65 and reducing the total nuclear entry of active p65. More importantly, we showed that a mutant EPEC/EHEC lacking both NleC and NleE (ΔnleC ΔnleE) caused greater inflammatory response than bacteria carrying ΔnleC or ΔnleE alone. This effect was similar to that of a T3SS-defective mutant. In conclusion, we found that NleC is an anti-inflammatory bacterial zinc protease, and that the cooperative function of NleE and NleC disrupts the NF-κB pathway and accounts for most of the immune suppression caused by EHEC/EPEC.

Dataset Information

Enterovirus 71 2C Protein Inhibits NF-?B Activation by Binding to RelA(p65).

Publications

Enterovirus 71 2C Protein Inhibits NF-κB Activation by Binding to RelA(p65).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets