Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I Activation under Simulated Microgravity

Zhu, Lv‐yun; Nie, Li; Xie, Shuhong; Li, Ming; Zhu, Chushu; Kuang, Jingyu; Liu, Chuanyang; Lu, Chenyu; Li, Wenying; Meng, Er; Zhang, Dongyi; Zhu, Lingyun

doi:10.1016/j.celrep.2020.108600

Cited by 13 publications

(8 citation statements)

References 78 publications

(72 reference statements)

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“…The TRIM25 function–induction positive feedback loop is essential in antiviral immunity, and the reduced TRIM25 expression under s-µ g interferes with the feedback loop. This model improves the current knowledge about host antiviral immunity in s-µ g [ 149 ]. An overview of all results is given in Table 5 .…”

Section: Resultsmentioning

confidence: 67%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 67%

“…Finally, Zhu et al [ 149 ] introduced a ground-based zebrafish disease model of µ g using an RCCS. RNA seq analysis revealed that s-µ g significantly influenced the retinoic-acid-inducible gene (RIG)-I-like receptor (RLR) and the Toll-like receptor (TLR) signaling pathways.…”

Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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“…The dataset used in this study was generated by the authors (hereby referred to as "the authors") of the paper titled "Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I activation under Simulated Microgravity" 17 . The methods used by the authors to generate the data were as follows.…”

Section: Methodsmentioning

confidence: 99%

“…In this review, we wanted to investigate the effects of simulated microgravity on vital biological pathways like DDR. To explore ways in which simulated microgravity affects biological function, we selected a study where zebrafish embryos were exposed to simulated microgravity conditions 17 . Although humans are very different from zebrafish, it was found that over 70% of the genes found in humans are also found in zebrafish 18 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic analysis of DNA damage response in zebrafish embryos under simulated microgravity

Barua

Komissarov

Kaur

et al. 2021

Preprint

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Objective: The objective of this study is to study the transcriptome of zebrafish embryos subjected to simulated microgravity and explore affected biological pathways, especially DNA damage response (DDR). The research question is whether simulated microgravity can have an impact on the basic biology of cell division, DNA repair, inflammation, and other vital cellular mechanisms. To validate that such experiments can yield relevant insights into human health and microgravity, we will correlate the found effects of simulated microgravity on zebrafish embryos with the reported effects of spaceflight on astronauts. Methods: 12 wild-type zebrafish embryos of both sexes, and of 3 to 12 months of age were microinjected with 2 nL (1 μg/μL) poly I:C or mock PBS buffer (0.5% phenol red, 240 mM KCl, and 40 mM HEPES at pH 7.4) using a microinjector followed by subjecting them immediately to the simulated microgravity conditions generated by RCCS or the normal gravity conditions in a cell culture dish. RNA-SEQ was performed on the samples according to the standard protocol. Raw gene counts data were obtained from the public domain (NASA Gene Labs) and subjected to further downstream analyses. Differential gene expression was performed using DESeq2. The results were annotated using pathway enrichment analysis (GSEA) on the KEGG pathway database and compared with the result of the NASA twin study. Result: Similar to previously published analysis, we found that a significant number of genes were differentially expressed under simulated microgravity conditions. We identified a total of 7542 genes out of 16532 when comparing expression between the groups: simulated microgravity and normal gravity (padj. value <0.05, log2 fold change in between -2 and 2). Out of these genes, 4504 were found to be up-regulated while 3038 were down-regulated compared to controls. Pathway enrichment analysis revealed that simulated microgravity has an effect on vital basic biological processes like DNA repair, peptide transport, and metabolism. Various other well-known signalling pathways like Notch signalling, wnt signalling, and p53 signalling were also significantly altered. These pathways are known to play an important role in DDR. To explore if the same pathways were also altered in humans, we explored the NASA twin study data and found that DDR was also significantly affected in the astronaut but due to ionizing radiation. Upon further investigation, we found that 62 genes belonging to the DDR pathway were mutually differentially expressed in Scott Kelly and the zebrafish embryos. However, there were 29 significantly differentially expressed genes belonging to the DDR pathway in zebrafish embryos that were not found to be differentially expressed in Scott Kelly. Out of these 29 genes, 14 were specific to zebrafish. Upon further investigation, we found that the DDR pathway is affected differently in simulated microgravity as compared to ionizing radiation. Conclusion: Simulated microgravity alters numerous biological pathways in zebrafish embryos, including DDR. But the nature of it is different from that of real spaceflight induced DDR. These observations should be investigated further to actually understand the nature of DNA damage response during spaceflights.

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“…It has been reported that the immune system is one of the most severely affected systems during space flight [9,10], and an impaired immune system can pose a serious threat to the health of astronauts. Zhu et al found that the retinoic-acid-inducible gene-I-like receptor (RLR) and Toll-like receptor (TLR) signalling pathways necessary for antiviral innate immunity were significantly inhibited in a microgravity environment, resulting in a dysfunctional antiviral immune response [11]. Bacterial or viral infections occurred in more than half of the astronauts on the Apollo mission, the first human mission to space in 1969.…”

Section: Introductionmentioning

confidence: 99%

Microgravity and immune cells

Yang

Jiang

et al. 2023

J. R. Soc. Interface.

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The microgravity environment experienced during spaceflight severely impaired immune system, making astronauts vulnerable to various diseases that seriously threaten the health of astronauts. Immune cells are exceptionally sensitive to changes in gravity and the microgravity environment can affect multiple aspects of immune cells through different mechanisms. Previous reports have mainly summarized the role of microgravity in the classification of innate and adaptive immune cells, lacking an overall grasp of the laws that microgravity effects on immune cells at different stages of their entire developmental process, such as differentiation, activation, metabolism, as well as function, which are discussed and concluded in this review. The possible molecular mechanisms are also analysed to provide a clear understanding of the specific role of microgravity in the whole development process of immune cells. Furthermore, the existing methods by which to reverse the damage of immune cells caused by microgravity, such as the use of polysaccharides, flavonoids, other natural immune cell activators etc. to target cell proliferation, apoptosis and impaired function are summarized. This review will provide not only new directions and ideas for the study of immune cell function in the microgravity environment, but also an important theoretical basis for the development of immunosuppression prevention and treatment drugs for spaceflight.

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Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I Activation under Simulated Microgravity

Cited by 13 publications

References 78 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

Transcriptomic analysis of DNA damage response in zebrafish embryos under simulated microgravity

Microgravity and immune cells

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