The Amino Acid at Position 95 in the Matrix Protein of Rabies Virus Is Involved in Antiviral Stress Granule Formation in Infected Cells

Kojima, Isshu; Onomoto, Koji; Zuo, Wenjie; Ozawa, Makoto; Okuya, Kosuke; Naitou, Kiyotada; Izumi, Fumiki; Okajima, Misuzu; Fujiwara, Takuro; Ito, Naoto; Yoneyama, Mitsutoshi; Yamada, Kentaro; Nishizono, Akira; Sugiyama, Makoto; Fujita, Takashi; Matsui, Tsutomu

doi:10.1128/jvi.00810-22

Cited by 3 publications

(2 citation statements)

References 67 publications

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“…No effective approach is available for rabies therapy once clinical symptoms occur [ 7 ]. Although the pathogenesis of rabies virus has been extensively studied, including functional determinants [ 8 , 9 , 10 , 11 ], innate immune response [ 12 , 13 ], and neuron death [ 4 , 14 ], currently, the pathogenic mechanism by which RABV causes host disease is unclear. The host immune system can recognize viruses as foreign matter and activate signal transduction pathways to clear them.…”

Section: Introductionmentioning

confidence: 99%

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Yu,

Jin,

Liu

et al. 2024

IJMS

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Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin–eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53–95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1β, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.

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Section: Introductionmentioning

confidence: 99%

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Yu,

Jin,

Liu

et al. 2024

IJMS

View full text Add to dashboard Cite

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“…In addition, the M protein interacts with RelAp43 to modulate the NF-κB pathway and, moreover, cooperates with the P protein to modulate the Jak-Stat pathway, thus contributing to viral immune evasion [ 11 , 12 , 13 ]. Lastly, the M protein is essential to induce host cell apoptosis and is thought to be one of the determinants of virus pathogenesis [ 14 , 15 , 16 ]. It should be noted that most of the diverse functions of the M protein are achieved by its interaction and recruitment of specific host factors.…”

Section: Introductionmentioning

confidence: 99%

Host Desmin Interacts with RABV Matrix Protein and Facilitates Virus Propagation

Wen

Liu

et al. 2023

Viruses

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Microfilaments and microtubules, two crucial structures of cytoskeletal networks, are usurped by various viruses for their entry, egress, and/or intracellular trafficking, including the Rabies virus (RABV). Intermediate filaments (IFs) are the third major component of cytoskeletal filaments; however, little is known about the role of IFs during the RABV infection. Here, we identified the IF protein desmin as a novel host interactor with the RABV matrix protein, and we show that this physical interaction has a functional impact on the virus lifecycle. We found that the overexpression of desmin facilitates the RABV infection by increasing the progeny virus yield, and the suppression of endogenous desmin inhibits virus replication. Furthermore, we used confocal microscopy to observe that the RABV-M co-localizes with desmin in IF bundles in the BHK-21 cells. Lastly, we found that mice challenged with RABV displayed an enhanced expression of desmin in the brains of infected animals. These findings reveal a desmin/RABV-M interaction that positively regulates the virus infection and suggests that the RABV may utilize cellular IFs as tracks for the intracellular transport of viral components and efficient budding.

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The roles of rabies virus structural proteins in immune evasion and implications for vaccine development

Wang,

Xing

2024

Can. J. Microbiol.

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Rabies is a zoonotic infectious disease that targets the nervous system of human and animals and has about 100% fatality rate without treatment. Rabies virus is a bullet-like viral particle composed of five structural proteins, including nucleoprotein (N), phosphorylated protein (P), matrix protein (M), glycoprotein (G), and large subunit (L) of RNA-dependent RNA polymerase. These multifunctional viral proteins also play critical roles in the immune escape by inhibiting specific immune responses in the host, resulting in massive replication of the virus in the nervous system and abnormal behaviors of patients such as brain dysfunction and hydrophobia, which ultimately lead to the death of patients. Herein, the role of five structural proteins of rabies virus in the viral replication and immune escape and its implication for the development of vaccines were systemically reviewed, so as to shed light on the understanding of pathogenic mechanism of rabies virus.

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The Amino Acid at Position 95 in the Matrix Protein of Rabies Virus Is Involved in Antiviral Stress Granule Formation in Infected Cells

Abstract: Rabies virus (RABV) is a neglected zoonotic pathogen that causes lethal infections in almost all mammalian hosts, including humans. Recently, RABV has been reported to induce intracellular formation of stress granules (SGs), also known as platforms that activate innate immune responses.

Cited by 3 publications

References 67 publications

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Host Desmin Interacts with RABV Matrix Protein and Facilitates Virus Propagation

The roles of rabies virus structural proteins in immune evasion and implications for vaccine development

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