RT Journal Article SR Electronic(1) A1 Palus, Martin A1 Bílý, Tomáš A1 Elsterová, Jana A1 Langhansová, Helena A1 Salát, Jiří A1 Vancová, Marie A1 Růžek, DanielYR 2014 T1 Infection and injury of human astrocytes by tick-borne encephalitis virus JF Journal of General Virology, VO 95 IS 11 SP 2411 OP 2426 DO https://doi.org/10.1099/vir.0.068411-0 PB Microbiology Society, SN 1465-2099, AB Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents the most important flaviviral neural infection in Europe and north-eastern Asia. In the central nervous system (CNS), neurons are the primary target for TBEV infection; however, infection of non-neuronal CNS cells, such as astrocytes, is not well understood. In this study, we investigated the interaction between TBEV and primary human astrocytes. We report for the first time, to the best of our knowledge, that primary human astrocytes are sensitive to TBEV infection, although the infection did not affect their viability. The infection induced a marked increase in the expression of glial fibrillary acidic protein, a marker of astrocyte activation. In addition, expression of matrix metalloproteinase 9 and several key pro-inflammatory cytokines/chemokines (e.g. tumour necrosis factor α, interferon α, interleukin (IL)-1β, IL-6, IL-8, interferon γ-induced protein 10, macrophage inflammatory protein, but not monocyte chemotactic protein 1) was upregulated. Moreover, we present a detailed description of morphological changes in TBEV-infected cells, as investigated using three-dimensional electron tomography. Several novel ultrastructural changes were observed, including the formation of unique tubule-like structures of 17.9 ±0.15 nm diameter with associated viral particles and/or virus-induced vesicles and located in the rough endoplasmic reticulum of the TBEV-infected cells. This is the first demonstration that TBEV infection activates primary human astrocytes. The infected astrocytes might be a potential source of pro-inflammatory cytokines in the TBEV-infected brain, and might contribute to the TBEV-induced neurotoxicity and blood–brain barrier breakdown that occurs during TBE. The neuropathological significance of our observations is also discussed., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.068411-0