Nucleocytoplasmic Trafficking Perturbation Induced by Picornaviruses

Picornaviruses are positive-stranded RNA viruses. Even though replication and translation of their genome take place in the cytoplasm, these viruses evolved different strategies to disturb nucleocytoplasmic trafficking of host proteins and RNA. The major targets of picornavirus are the phenylalanine-glycine (FG)-nucleoporins, which form a mesh in the central channel of the nuclear pore complex through which protein cargos and karyopherins are actively transported in both directions. Interestingly, while enteroviruses use the proteolytic activity of their 2A protein to degrade FG-nucleoporins, cardioviruses act by triggering phosphorylation of these proteins by cellular kinases. By targeting the nuclear pore complex, picornaviruses recruit nuclear proteins to the cytoplasm, where they increase viral genome translation and replication; they affect nuclear translocation of cytoplasmic proteins such as transcription factors that induce innate immune responses and retain host mRNA in the nucleus thereby preventing cell emergency responses and likely making the ribosomal machinery available for translation of viral RNAs.

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A dual-role of SARS-CoV-2 nucleocapsid protein in regulating innate immune response

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00742-w ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Yinghua Zhao ◽

Liyan Sui ◽

Ping Wu ◽

Wenfang Wang ◽

Zedong Wang ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Inflammatory Cytokines ◽

Low Dose ◽

Nuclear Translocation ◽

Innate Immune ◽

High Dose ◽

Type I ◽

Innate Immune Responses ◽

N Protein

AbstractThe recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and overactive immune response in the late stage of infection; However, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein dually regulated the phosphorylation and nuclear translocation of IRF3, STAT1, and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress the ubiquitination and activation of retinoic acid-inducible gene I (RIG-I). Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

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Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1324140111 ◽

2014 ◽

Vol 111 (7) ◽

pp. 2650-2655 ◽

Cited By ~ 113

Author(s):

A.-M. Bulau ◽

M. F. Nold ◽

S. Li ◽

C. A. Nold-Petry ◽

M. Fink ◽

...

Keyword(s):

Immune Responses ◽

Nuclear Translocation ◽

Innate Immune ◽

Innate Immune Responses ◽

Caspase 1

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Lysosomal Protein Lamtor1 Controls Innate Immune Responses via Nuclear Translocation of Transcription Factor EB

The Journal of Immunology ◽

10.4049/jimmunol.1701283 ◽

2018 ◽

Vol 200 (11) ◽

pp. 3790-3800 ◽

Cited By ~ 5

Author(s):

Yoshitomo Hayama ◽

Tetsuya Kimura ◽

Yoshito Takeda ◽

Shigeyuki Nada ◽

Shohei Koyama ◽

...

Keyword(s):

Transcription Factor ◽

Immune Responses ◽

Nuclear Translocation ◽

Innate Immune ◽

Innate Immune Responses ◽

Transcription Factor Eb ◽

Lysosomal Protein

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SARS-CoV-2 nucleocapsid protein dually regulates innate immune responses

10.1101/2021.02.17.431755 ◽

2021 ◽

Author(s):

Yinghua Zhao ◽

Liyan Sui ◽

Ping Wu ◽

Wenfang Wang ◽

Guangyun Tan ◽

...

Keyword(s):

Immune Responses ◽

Inflammatory Cytokines ◽

Low Dose ◽

Nuclear Translocation ◽

Early Stage ◽

Innate Immune ◽

High Dose ◽

Type I ◽

Innate Immune Responses ◽

N Protein

ABSTRACTThe recently emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing global pandemic of COVID-19, may trigger immunosuppression in the early stage and a cytokine storm in the late stage of infection, however, the underlying mechanisms are not well understood. Here we demonstrated that the SARS-CoV-2 nucleocapsid (N) protein dually regulated innate immune responses, i.e., the low-dose N protein suppressed type I interferon (IFN-I) signaling and inflammatory cytokines, whereas high-dose N protein promoted IFN-I signaling and inflammatory cytokines. Mechanistically, the SARS-CoV-2 N protein interacted with the tripartite motif protein 25 (TRIM25), thereby dually regulating the phosphorylation and nuclear translocation of IRF3, STAT1 and STAT2. Additionally, low-dose N protein combined with TRIM25 could suppress retinoic acid-inducible gene I (RIG-I) ubiquitination and activation. Our findings revealed a regulatory mechanism of innate immune responses by the SARS-CoV-2 N protein, which would contribute to understanding the pathogenesis of SARS-CoV-2 and other SARS-like coronaviruses, and development of more effective strategies for controlling COVID-19.

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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