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

Lenz, Nicole; Engler, Olivier; Grandgirard, Denis; Leib, Stephen L.; Ackermann-Gäumann, Rahel (2018). Evaluation of antivirals against tick-borne encephalitis virus in organotypic brain slices of rat cerebellum. PLoS ONE, 13(10), e0205294. Public Library of Science 10.1371/journal.pone.0205294

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research

UniBE Contributor:

Lenz, Nicole; Grandgirard, Denis and Leib, Stephen

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1932-6203

Publisher:

Public Library of Science

Funders:

[4] Swiss National Science Foundation

Projects:

Projects 160780 not found.

Language:

English

Submitter:

Stephen Leib

Date Deposited:

16 Oct 2018 09:20

Last Modified:

18 Jun 2019 17:14

Publisher DOI:

10.1371/journal.pone.0205294

PubMed ID:

30300398

BORIS DOI:

10.7892/boris.120478

URI:

https://boris.unibe.ch/id/eprint/120478

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