The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620807
Title:
The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus.
Authors:
Asghar, Naveed; Lee, Yi-Ping; Nilsson, Emma; Lindqvist, Richard; Melik, Wessam; Kröger, Andrea; Överby, Anna K; Johansson, Magnus
Abstract:
The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Torö-2003 with the wild-type (A)3C(A)6 sequence (Torö-6A) or with a modified (A)3C(A)38 sequence (Torö-38A). Torö-38A replicated poorly compared to Torö-6A in cell culture, but Torö-38A was more virulent than Torö-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.
Affiliation:
Helmholtz Centre for infection research. Inhoffenstr. 7. 38124 Braunschweig, Germany.
Citation:
The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus. 2016, 6:39265 Sci Rep
Journal:
Scientific reports
Issue Date:
16-Dec-2016
URI:
http://hdl.handle.net/10033/620807
DOI:
10.1038/srep39265
PubMed ID:
27982069
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the research group immunity and infection (IMMI)

Full metadata record

DC FieldValue Language
dc.contributor.authorAsghar, Naveeden
dc.contributor.authorLee, Yi-Pingen
dc.contributor.authorNilsson, Emmaen
dc.contributor.authorLindqvist, Richarden
dc.contributor.authorMelik, Wessamen
dc.contributor.authorKröger, Andreaen
dc.contributor.authorÖverby, Anna Ken
dc.contributor.authorJohansson, Magnusen
dc.date.accessioned2017-02-03T14:05:20Z-
dc.date.available2017-02-03T14:05:20Z-
dc.date.issued2016-12-16-
dc.identifier.citationThe role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus. 2016, 6:39265 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid27982069-
dc.identifier.doi10.1038/srep39265-
dc.identifier.urihttp://hdl.handle.net/10033/620807-
dc.description.abstractThe tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Torö-2003 with the wild-type (A)3C(A)6 sequence (Torö-6A) or with a modified (A)3C(A)38 sequence (Torö-38A). Torö-38A replicated poorly compared to Torö-6A in cell culture, but Torö-38A was more virulent than Torö-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleThe role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research. Inhoffenstr. 7. 38124 Braunschweig, Germany.en
dc.identifier.journalScientific reportsen

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