Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Frelin L) > Immune-mediated eff...

Details
MARC

Levander, S (author)

Immune-mediated effects targeting hepatitis C virus in a syngeneic replicon cell transplantation mouse model

Article/chapterEnglish2018

Publisher, publication year, extent ...

2017-06-23
BMJ,2018

Numbers

LIBRIS-ID:oai:prod.swepub.kib.ki.se:139012120
http://kipublications.ki.se/Default.aspx?queryparsed=id:139012120URI
https://doi.org/10.1136/gutjnl-2016-313579DOI

Supplementary language notes

Language:English
Summary in:English

Part of subdatabase

SwePubSwePub

Classification

Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

HCV is characterised by its ability to establish chronic infection in hepatocytes and to replicate in the presence of an inflammation. We mimicked this situation in vivo in immune-competent mice by syngeneic transplantation of HCV replicon-containing mouse hepatoma cells.DesignA total of 5 million H-2b positive Hep56.1D cells, carrying a subgenomic genotype (gt) 2a replicon (HCV replicon cells) or stably expressing comparable levels of the HCV NS3/4A protease/helicase complex (NS3/4A hepatoma cells), were injected subcutaneously into syngeneic H-2b-restricted mice. Kinetics of tumour growth, HCV RNA replication levels and HCV-specific immune responses were monitored. For immune monitoring, new H-2b-restricted cytotoxic T cell epitopes within the gt2a NS3/4A region were mapped. Immune mice were generated by DNA-based vaccination.ResultsHCV replicon and NS3/4A hepatoma cells generated solid tumours in vivo. Similar to what is seen in human HCV infection did HCV RNA replicate in the presence of inflammation. NS3/4A-specific CD8+ T cells seemed to transiently reduce HCV RNA levels. Both CD4+ and CD8+ T cells were required for protection against tumour growth. Vaccine-induced NS3/4A(gt2a)-specific T cells protected against HCV replicon tumours in wild-type, but not in HCV NS3/4A(gt1a)-transgenic mice with dysfunctional HCV-specific T cells. Importantly, as in human HCV infection, HCV replicon cells neither primed nor boosted a strong NS3/4A-specific T cell response.ConclusionSyngeneic transplantation of mouse HCV replicon cells into immune-competent animals mirrors many in vivo events in humans. This system is versatile and can be applied to any genetically modified H-2b-restricted mouse strain.

Added entries (persons, corporate bodies, meetings, titles ...)

Holmstrom, F (author)
Frelin, LKarolinska Institutet (author)
Ahlen, GKarolinska Institutet (author)
Rupp, D (author)
Long, G (author)
Bartenschlager, R (author)
Sallberg, MKarolinska Institutet (author)
Karolinska Institutet (creator_code:org_t)

Related titles

In:Gut: BMJ67:8, s. 1525-15351468-32880017-5749

Internet link

Find in a library

Gut (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Levander, S; Holmstrom, F; Frelin, L; Ahlen, G; Rupp, D; Long, G; show more...; Bartenschlager, ...; Sallberg, M; show less...

Articles in the publication: Gut

By the university: Karolinska Institutet

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se