The effect of combined drugs therapy on the course of clinical rabies infection in a murine model

Smreczak, Marcin; Orłowska, Anna; Marzec, Anna; Trębas, Paweł; Kycko, Anna; Reichert, M.; Koraka, Penelope; Osterhaus, Albert D. M. E.; Zmudzinski, J.F.

doi:10.1016/j.vaccine.2018.04.003

Cited by 13 publications

(8 citation statements)

References 15 publications

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“…Pyroptosis is a type of cell death involving a strong inflammatory response that has been implicated in the development of many diseases. Previous studies showed that inhibition of the pro-inflammatory response associated with pyroptosis by inhibiting CASP-1 expression demonstrated a beneficial effect on the survival time of mice [ 30 , 31 , 32 ]. To sum up, in this study, we found that RABV infection causes pyroptosis of neuronal cells.…”

Section: Discussionmentioning

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: Discussionmentioning

confidence: 99%

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Yu,

Jin,

Liu

et al. 2024

IJMS

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“…Dermaseptins have been described as potential anti-rabies compounds in vitro and with 50–60% of survival gain in mice(Mechlia et al ., 2019). Drug cocktails containing Favipiravir, Ribavirin, Interferon α/β, a Caspase-1 inhibitor, a TNF-α inhibitor, a MAPKs inhibitor and human rabies immune globulin (HRIG) have been explored in mouse RABV models (Smreczak et al ., 2019) but no clear therapeutic effect was noted. A cocktail of two human monoclonal antibodies RVC20/RVC58 delivered directly into the brain could cure half of the symptomatic rabid mice in the research(de Melo et al ., 2020).…”

Section: Discussionmentioning

confidence: 99%

TheUrtica DioicaAgglutinin Prevents Rabies Virus Infection in a Muscle Explant Model

Wang

Terrie

et al. 2021

Preprint

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Infection with the rabies virus (RABV) causes fatal encephalitis and paralysis in humans and animals. Post-exposure prophylaxis (PEP) consists of vaccination and the injection of anti-rabies immunoglobulins (RIGs) around the (bite) wound. This is 100% effective in preventing disease if administered in a timely manner. However, the costs, the required cold chain for storage and transport and the limited availability of RIGs makes the treatment challenging. Cheaper and easier to produce alternatives are urgently needed. To aid in the discovery and development of such alternative therapeutics, we developed a physiological relevant infection model. Strips of freshly dissected swine skeletal muscle were placed under tension in culture medium and infected with RABV. Viral antigens were produced in the muscle explants and the virus production increased significantly over time, indicating that RABV infects and replicates in the muscle explants. Subsequently, in a search for inhibitors of RABV entry in muscle cells, we first screened a panel of 34 different lectins in a RABV / BHK-21J cell assay. The Urtica Dioica (stinging nettle) Agglutinin (UDA; a N-acetyl-D-glucosamine specific agglutinin) was found to be able to completely inhibit infection of cells with the RABV (EC50 8.2 μg/mL) by preventing binding of the virus to the host cell. When the infection of the muscle strips was carried out in the presence of UDA, infection of the tissue was completely prevented. We thus developed a physiological relevant RABV muscle infection model and identified an easy to produce component that (i) may serve as a reference for further studies and (ii) holds promise as an alternative for RIGs in PEP.

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“…Common components for traditional prevention and treatment of neurotropic viruses include vaccines and antiviral drugs to promote the host antiviral innate and adaptive immunity for viral clearance ( Vere Hodge and Field, 2013 ; Kamiyama et al, 2017 ; Smreczak et al, 2019 ).…”

Section: Conventional Prevention and Treatment Of Neurotropic Viral Infectionmentioning

confidence: 99%

Functionalized Nanoparticles in Prevention and Targeted Therapy of Viral Diseases With Neurotropism Properties, Special Insight on COVID-19

et al. 2021

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Neurotropic viruses have neural-invasive and neurovirulent properties to damage the central nervous system (CNS), leading to humans’ fatal symptoms. Neurotropic viruses comprise a lot of viruses, such as Zika virus (ZIKV), herpes simplex virus (HSV), rabies virus (RABV), and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). Effective therapy is needed to prevent infection by these viruses in vivo and in vitro. However, the blood-brain barrier (BBB) usually prevents macromolecules from entering the CNS, which challenges the usage of the traditional probes, antiviral drugs, or neutralizing antibodies in the CNS. Functionalized nanoparticles (NPs) have been increasingly reported in the targeted therapy of neurotropic viruses due to their sensitivity and targeting characteristics. Therefore, the present review outlines efficient functionalized NPs to further understand the recent trends, challenges, and prospects of these materials.

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The effect of combined drugs therapy on the course of clinical rabies infection in a murine model

Cited by 13 publications

References 15 publications

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells

TheUrtica DioicaAgglutinin Prevents Rabies Virus Infection in a Muscle Explant Model

Functionalized Nanoparticles in Prevention and Targeted Therapy of Viral Diseases With Neurotropism Properties, Special Insight on COVID-19

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