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

Naveed Asghar, Yi Ping Lee, Emma Nilsson, Richard Lindqvist, Wessam Melik, Andrea Kröger, Anna K. Överby, Magnus Johansson

研究成果: Article同行評審

27 引文 斯高帕斯(Scopus)

摘要

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)3 C(A)6 sequence (Torö-6A) or with a modified (A)3 C(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.

原文English
文章編號39265
期刊Scientific reports
6
DOIs
出版狀態Published - 2016 12月 16

All Science Journal Classification (ASJC) codes

  • 多學科

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