The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling

Li, Siji; Kuang, Ming; Chen, Luoying; Li, Yunfei; Liu, Shengde; Du, Hongqiang; Cao, Lili; You, Fangtian

doi:10.1016/j.celrep.2020.108631

Cited by 30 publications

(25 citation statements)

References 75 publications

(91 reference statements)

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“…COG6 and SERINC4 have been suggested to be inhibitors of HIV-1 replication ( Liu et al, 2014 ; Qiu et al, 2020 ), while the expression of AZGP1 , which has been reported to be associated with HPV status, was significantly high ( Poropatich et al, 2019 ). ERAL1 suppressed RNA virus infection by facilitating RIG-I-like receptor signaling ( Li et al, 2021 ), while ORMDL3 was reported to be regulated by IRF-3 as a result of RSV infection by direct binding to the promoter of ORMDL3 ( Wang et al, 2017 ). Evidently, STAT2 , as a transcription regulatory factor, could increase the levels of the interferon-stimulated gene (ISG) and IFN transcripts in response to RV, establishing an antiviral state ( Angel et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves

Elkady

Chen

et al. 2022

Front. Microbiol.

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Bovine rotavirus (BRV) causes massive economic losses in the livestock industry worldwide. Elucidating the pathogenesis of BRV would help in the development of more effective measures to control BRV infection. The MA-104 cell line is sensitive to BRV and is thereby a convenient tool for determining BRV–host interactions. Thus far, the role of the microRNAs (miRNAs) of MA-104 cells during BRV infection is still ambiguous. We performed Illumina RNA sequencing analysis of the miRNA libraries of BRV-infected and mock-infected MA-104 cells at different time points: at 0 h post-infection (hpi) (just after 90 min of adsorption) and at 6, 12, 24, 36, and 48 hpi. The total clean reads obtained from BRV-infected and uninfected cells were 74,701,041 and 74,184,124, respectively. Based on these, 579 were categorized as known miRNAs and 144 as novel miRNAs. One hundred and sixty differentially expressed (DE) miRNAs in BRV-infected cells in comparison with uninfected MA-104 cells were successfully investigated, 95 of which were upregulated and 65 were downregulated. The target messenger RNAs (mRNAs) of the DE miRNAs were examined by bioinformatics analysis. Functional annotation of the target genes with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested that these genes mainly contributed to biological pathways, endocytosis, apoptotic process, trans-Golgi membrane, and lysosome. Pathways such as the mammalian target of rapamycin (mTOR) (mml-miR-486-3p and mml-miR-197-3p), nuclear factor kappa B (NF-κB) (mml-miR-204-3p and novel_366), Rap1 (mml-miR-127-3p), cAMP (mml-miR-106b-3p), mitogen-activated protein kinase (MAPK) (mml-miR-342-5p), T-cell receptor signaling (mml-miR-369-5p), RIG-I-like receptor signaling (mml-miR-504-5p), AMP-activated protein kinase (AMPK) (mml-miR-365-1-5p), and phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling (mml-miR-299-3p) were enriched. Moreover, real-time quantitative PCR (qPCR) verified the expression profiles of 23 selected DE miRNAs, which were consistent with the results of deep sequencing, and the 28 corresponding target mRNAs were mainly of regulatory pathways of the cellular machinery and immune importance, according to the bioinformatics analysis. Our study is the first to report a novel approach that uncovers the impact of BRV infection on the miRNA expressions of MA-104 cells, and it offers clues for identifying potential candidates for antiviral or vaccine strategies.

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Section: Discussionmentioning

confidence: 99%

MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves

Elkady

Chen

et al. 2022

Front. Microbiol.

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“…Protrusion of the IMM through OMM pores generated during MOMP allows for release of immunogenic mitochondrial matrix components, such as mtDNA, mtdsRNA, and ERAL1. While mtdsRNA ( 106 ) and ERAL1 ( 107 ) induce MAVS signaling, mtDNA release activates the cGAS/STING pathway ( 74 , 75 ), the NLRP3 ( 93 – 96 ) and AIM2 (not shown) ( 75 , 97 ) inflammasome pathways, and TLR9 ( 91 ) signaling. Importantly, caspase-3 cleavage of cGAS and IRF3 regulates whether MOMP leads to inflammatory signaling or apoptosis ( 81 – 83 ).…”

Section: Activation Of Mitochondrial Cell Death Pathways During Viral Infectionsmentioning

confidence: 99%

“…coli Ra s- l ike 1 (ERAL1) during RNA virus infection by BAX/BAK enhances MAVS signaling in vitro and in vivo during RNA virus infection ( Fig. 1C ) ( 107 ). This ERAL1 activity is RIG-I dependent.…”

Section: Mitochondrial Regulation Of Immune Gene Expression Programs During Viral Infectionmentioning

confidence: 99%

“…Consistently, ERAL1 knockdown in THP-1, HT-29, HEK293T, and HeLa cells attenuates IFNβ production during RNA virus infection. A physiological role for ERAL1 is apparent as Eral +/- mice are more susceptible to RNA virus infection-associated lethality than the control Eral +/+ mice ( 107 ).…”

Section: Mitochondrial Regulation Of Immune Gene Expression Programs During Viral Infectionmentioning

confidence: 99%

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Mitochondria and Viral Infection: Advances and Emerging Battlefronts

Sorouri

Chang

Hancks

2022

mBio

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“…SARS-CoV-2 infection activates pattern recognition receptors on pulmonary epithelial cells, endothelial cells, macrophages, DCs, and other immune cells to produce cytokines [ 96 , 97 ]. Recognition receptors including Toll-like receptors (TLRs), retinoic acid-inducible gene I (RIG-I, melanoma differentiation-associated gene 5 (MDA5), cyclic guanosine phosphate adenosine phosphate synthase (cGAS), stimulator of interferon genes (STING), and nucleotide-binding oligomerization domain-like receptors (NLRs) play a significant role in antiviral defense against coronaviruses ( Figure 3 ) [ 98 , 99 , 100 ].…”

Section: Ace2 Sars-cov-2 and Innate Immune Pathwaysmentioning

confidence: 99%

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

Chen

Yin

et al. 2021

IJMS

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Despite the protracted battle against coronavirus acute respiratory infection (COVID-19) and the rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), no specific and effective drugs have to date been reported. Angiotensin-converting enzyme 2 (ACE2) is a zinc metalloproteinase and a critical modulator of the renin-angiotensin system (RAS). In addition, ACE2 has anti-inflammatory and antifibrosis functions. ACE has become widely known in the past decade as it has been identified as the primary receptor for SARS-CoV and SARS-CoV-2, being closely associated with their infection. SARS-CoV-2 primarily targets the lung, which induces a cytokine storm by infecting alveolar cells, resulting in tissue damage and eventually severe acute respiratory syndrome. In the lung, innate immunity acts as a critical line of defense against pathogens, including SARS-CoV-2. This review aims to summarize the regulation of ACE2, and lung host cells resist SARS-CoV-2 invasion by activating innate immunity response. Finally, we discuss ACE2 as a therapeutic target, providing reference and enlightenment for the clinical treatment of COVID-19.

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The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling

Cited by 30 publications

References 75 publications

MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves

MicroRNA Profile of MA-104 Cell Line Associated With the Pathogenesis of Bovine Rotavirus Strain Circulated in Chinese Calves

Mitochondria and Viral Infection: Advances and Emerging Battlefronts

ACE2 and Innate Immunity in the Regulation of SARS-CoV-2-Induced Acute Lung Injury: A Review

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