Trim25 restricts rabies virus replication by destabilizing phosphoprotein

Yuan, Yueming; Fang, An; Wang, Zongmei; Tian, Bin; Zhang, Yuan; Sui, Baokun; Luo, Zhidan; Li, Yingying; Zhou, Ming; Chen, Huanchun; Fu, Zhen F.; Zhao, Ling

doi:10.1016/j.cellin.2022.100057

Cited by 12 publications

(11 citation statements)

References 60 publications

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“…The biological characteristics of different strains of rabies virus differ, as has been documented in other studies [56,57], showing that the effects of different strains on autophagy could be opposite. It is likely that the discrepancy between our and Yuan's findings [55] may be due to the different strains used, although we could not rule out other possibilities. However, for the direct antiviral activity mediated by TRIM proteins, there may be an indirect mechanism between the host and a TRIM protein.…”

Section: Discussioncontrasting

confidence: 84%

TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons

Zhang

Cai

et al. 2023

Genes

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Rabies remains a great threat to public health worldwide. So far, the mechanism of rabies virus (RABV) infection is not fully understood, and there is no effective treatment for rabies. Identifying more host restriction factors of RABV will spur the development of novel therapeutic interventions against rabies. Accumulating studies suggest that tripartite motif-containing (TRIM) proteins have great effects on virus replication. TRIMs control the antiviral responses through either direct interaction with viral proteins or indirect regulation of innate immune signaling molecules in the host. The role of TRIM25 in rabies virus (RABV) infection is poorly understood. Using next-generation sequencing, we found that TRIM25 is upregulated during HEP-Flury infection. Knockdown of TRIM25 enhances HEP-Flury production, while overexpression of TRIM25 suppresses HEP-Flury replication. Knockdown of interferon α and interferon β weakens the anti-RABV response induced by TRIM25 overexpression, and potentiates RABV production. Furthermore, we found that TRIM25 regulates type-I interferon response by targeting retinoic acid-inducible gene I (RIG-I) during HEP-Flury infection. Knockdown of RIG-I weakens the anti-HEP-Flury response induced by TRIM25 overexpression, indicating that TRIM25 regulates RABV production via the RIG-I-IFN axis. In addition, we observed that TRIM25 does not directly interact with HEP-Flury structural proteins, suggesting that TRIM25 regulates HEP-Flury production indirectly. Taken together, our work identifies TRIM25 as a new host factor involved in HEP-Flury infection, which may be a potential target for the development of antiviral drugs against RABV.

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Section: Discussioncontrasting

confidence: 84%

TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons

Zhang

Cai

et al. 2023

Genes

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“…Lab-attenuated RABV strain CVS-B2c (derived from CVS-24 by passaging in BHK-21 cells) and wt RABV strain of DRV-Mexico (DRV) were stored in our laboratory. The recombinant RABVs were cloned from CVS-B2c, and the recombinant CVS and CVS-GFP-P were constructed as described previously ( 46 ).…”

Section: Methodsmentioning

confidence: 99%

“…Recombinant RABVs were rescued as reported previously ( 46 ). Briefly, N2a cells were transfected with 2 µg of a fully infectious clone (pcDNA3.1-CVS or pcDNA3.1-CVS-M-G57E), 0.5 µg of pcDNA3.1-N, 0.25 µg of pcDNA3.1-P, 0.15 µg of pcDNA3.1-G, and 0.1 µg of pcDNA3.1-L using jetPRIME (Polyplus) according to the manufacturer’s instruction.…”

Section: Methodsmentioning

confidence: 99%

Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism

Yuan,

Fang,

Wang

et al. 2024

mBio

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Previous studies have suggested that RABV (rabies virus, the representative of lyssavirus) infection induces structural abnormalities in neurons. But there are few articles on the mechanism of lyssavirus’ effect on neurons, and the mechanism of how RABV infection induces neurological dysfunction remains incomplete. The M protein of lyssavirus can downregulate cellular ATP levels by interacting with Slc25a4, and this decrease in ATP leads to a decrease in the level of NAD + in the cytosol, which results in the release of Ca 2+ from the intracellular calcium pool, the endoplasmic reticulum, and mitochondria. The presence of large amounts of Ca 2+ in the cytoplasm activates Ca 2+ -dependent proteases and degrades microtubule proteins. The amino acid 57 of M protein is the key site determining its disruption of mitochondrial metabolism and subsequent neuron degeneration.

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“…The procedure applied for RABV titration was determined by direct immunofluorescence assay using FITC-conjugated anti-RABV N antibody (Fujirebio Diagnostics, Malvern, PA) as described previously [ 48 ].…”

Section: Methodsmentioning

confidence: 99%

The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis

et al. 2023

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Trim25 restricts rabies virus replication by destabilizing phosphoprotein

Cited by 12 publications

References 60 publications

TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons

TRIM25 Suppresses Rabies Virus Fixed HEP-Flury Strain Production by Activating RIG-1-Mediated Type I Interferons

Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism

The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis

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