A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

Maffioli, Carola; Grandgirard, Denis; Engler, Olivier; Leib, Stephen L.

doi:10.1097/nen.0000000000000131

Cited by 22 publications

(29 citation statements)

References 42 publications

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“…OCS were stained for TBEV using a red fluorescent dye and for two abundant cell types present in the OCS, namely Purkinje cells and mature neurons in green ( Fig 4 for Purkinje cells and S4 Fig for mature neurons). Similar to observations made with the TBEV model virus Langat [ 12 ], TBEV partially co-localized within Purkinje cells, the largest neurons present in the cerebellum (see S5 Fig for a close-up view). As expected, in OCS treated with 2'-CMA and 7-deaza-2'-CMA no TBEV could be detected, whereas in OCS treated with 2'-CMC and Ribavirin the fluorescent signal for TBEV was comparable to the controls.…”

Section: Resultssupporting

confidence: 82%

“…Purkinje cells were identified as the main cell type infected by a TBEV model virus in the cerebellum [ 12 ]. Since Purkinje cells are most abundant and polarized in the brain of 10 days-old pups [ 14 ], we euthanized 10 days-old Wistar rats (Charles River Laboratories, Sulzfeld, Germany) by a lethal dose of intraperitoneal pentobarbital (G. Streuli & Cie. SA, Uznach, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

“…Cell lines enable screening of large libraries of antiviral compounds, yet the results vary considerably between different cell types [ 11 ]. Therefore we developed rat organotypic cerebellum slices (OCS), representing the primary target site for TBEV infection in the brain [ 12 ]. The natural anatomy of the cerebellum is conserved in OCS.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum

et al. 2018

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Neurotropic tick borne encephalitis virus (TBEV) causes life-threatening disease, and accounts for most cases of tick-transmitted viral infections in Central and Eastern Europe and Russia. No specific treatment for TBEV infections exists, and vaccination is recommended for people at risk. So far, various nucleoside analogues have been investigated in vitro as potential candidates for treatment of TBEV infections. However, in vitro experiments with more complex cell culture systems, such as organotypic culture slices which model the sophisticated architecture of the target tissue are lacking. Using TBEV as a model, we investigated the suitability of rat organotypic cerebellum slices (OCS) to study the effectiveness of nucleoside analogues with a well-known anti-TBEV activity. In these OCS, 50 μM of the nucleoside analogues 2’-C-methyladenosine (2’-CMA) and especially 7-deaza-2’-C-methyladenosine (7-deaza-2’-CMA) exhibited strong inhibitory effects on TBEV replication, reducing viral titers to an average of 103-fold and TBEV RNA content 60-90-fold. In contrast, the influence of 2’-C-methylcytidine (2’-CMC) on TBEV replication was very weak, reducing virus titers by 10-fold and TBEV RNA content by 3-fold. In agreement with other studies, there was no noticeable difference in TBEV titers between OCS treated with 50 μM of Ribavirin and the DMSO treated controls. All tested nucleoside analogues exhibited excellent cytotoxicity profiles at concentrations of 50 μM. Our findings in OCS were highly comparable to data obtained in cell line culture systems. Therefore, OCS represent an ideal in vitro approach to study antivirals against TBEV and possibly other neurotropic viruses.

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Section: Resultssupporting

confidence: 82%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum

et al. 2018

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“…Several neurotropic viruses have been shown to induce microglia activation in the CNS following infection, including Japanese encephalitis virus [ 43 , 44 ], Dengue Virus [ 45 ], Zika virus [ 46 ], Tick-borne encephalitis virus [ 47 ], reovirus [ 48 ], and mouse hepatitis virus [ 49 , 50 ]. Evidence that microglia are activated during WNV-induced CNS disease in humans includes the presence of microglial nodules and increased proliferation [ 51 , 52 ].…”

Section: Microglia Become Activated During Wnv Infectionmentioning

confidence: 99%

The Role of Microglia during West Nile Virus Infection of the Central Nervous System

2020

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Encephalitis resulting from viral infections is a major cause of hospitalization and death worldwide. West Nile Virus (WNV) is a substantial health concern as it is one of the leading causes of viral encephalitis in the United States today. WNV infiltrates the central nervous system (CNS), where it directly infects neurons and induces neuronal cell death, in part, via activation of caspase 3-mediated apoptosis. WNV infection also induces neuroinflammation characterized by activation of innate immune cells, including microglia and astrocytes, production of inflammatory cytokines, breakdown of the blood-brain barrier, and infiltration of peripheral leukocytes. Microglia are the resident immune cells of the brain and monitor the CNS for signs of injury or pathogens. Following infection with WNV, microglia exhibit a change in morphology consistent with activation and are associated with increased expression of proinflammatory cytokines. Recent research has focused on deciphering the role of microglia during WNV encephalitis. Microglia play a protective role during infections by limiting viral growth and reducing mortality in mice. However, it also appears that activated microglia are triggered by T cells to mediate synaptic elimination at late times during infection, which may contribute to long-term neurological deficits following a neuroinvasive WNV infection. This review will discuss the important role of microglia in the pathogenesis of a neuroinvasive WNV infection. Knowledge of the precise role of microglia during a WNV infection may lead to a greater ability to treat and manage WNV encephalitis.

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“…Flaviviruses have the ability to infect Ixodid ticks at any developmental stage (larvae, nymphs or adults), and the infection can be maintained throughout the tick's lifespan 20,22,24 . Tick-borne flaviviruses usually spend 95% of their life cycle in Ixodes tick vector than in the vertebrate host including accidental human host 25 .…”

Section: Introductionmentioning

confidence: 99%

An Experimental Murine Model to Study Acquisition Dynamics of Tick-Borne Langat Virus in Ixodes Scapularis

Rajendran

Ahmed

Roozitalab

et al. 2021

Preprint

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Ixodes scapularis ticks acquire several pathogens from reservoir animals and transmit them to humans. Development of an animal model to study acquisition and transmission dynamics of these pathogens into and from ticks, respectively, is challenging due to the fact that in nature ticks feed for a longer duration and on multiple vertebrate hosts. To understand the complex nature of pathogen acquisition/transmission, it is essential to set up a successful tick blood feeding method on a suitable vertebrate host. In this study, we provide an evidence that murine model can be successfully used to study acquisition dynamics of Langat virus (LGTV), a member of tick-borne flaviviruses. Mice were inoculated intraperitoneally with LGTV that showed detectable viral loads in murine blood, skin and other tissues including brain. Both larval and nymphal ticks that were allowed to feed on murine host successfully acquired LGTV loads. Also, we found that after molting LGTV was transstadially transmitted from larval to nymphal stage. In addition, we noted that, LGTV down-regulated IsSMase expression in all group of ticks possibly for its survival in its vector host. Taken together, we provide an evidence on the use of murine model to not only study acquisition dynamics of LGTV but also to study changes in tick gene expression during acquisition of arboviruses into ticks.

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A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

Cited by 22 publications

References 42 publications

Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum

Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum

The Role of Microglia during West Nile Virus Infection of the Central Nervous System

An Experimental Murine Model to Study Acquisition Dynamics of Tick-Borne Langat Virus in Ixodes Scapularis

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