Dataset Information

Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons.

ABSTRACT: Tick-borne encephalitis virus (TBEV) causes serious, potentially fatal neurological infections that affect humans in endemic regions of Europe and Asia. Neurons are the primary target for TBEV infection in the central nervous system. However, knowledge about this viral infection and virus-induced neuronal injury is fragmental. Here, we directly examined the pathology that occurs after TBEV infection in human primary neurons. We exploited the advantages of advanced high-pressure freezing and freeze-substitution techniques to achieve optimal preservation of infected cell architecture. Electron tomographic (ET) reconstructions elucidated high-resolution 3D images of the proliferating endoplasmic reticulum, and individual tubule-like structures of different diameters in the endoplasmic reticulum cisternae of single cells. ET revealed direct connections between the tubule-like structures and viral particles in the endoplasmic reticulum. Furthermore, ET showed connections between cellular microtubules and vacuoles that harbored the TBEV virions in neuronal extensions. This study was the first to characterize the 3D topographical organization of membranous whorls and autophagic vacuoles in TBEV-infected human neurons. The functional importance of autophagy during TBEV replication was studied in human neuroblastoma cells; stimulation of autophagy resulted in significantly increased dose-dependent TBEV production, whereas the inhibition of autophagy showed a profound, dose-dependent decrease of the yield of infectious virus.

SUBMITTER: Bily T

PROVIDER: S-EPMC4466586 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons.

Bílý Tomáš T Palus Martin M Eyer Luděk L Elsterová Jana J Vancová Marie M Růžek Daniel D

Scientific reports 20150615

Tick-borne encephalitis virus (TBEV) causes serious, potentially fatal neurological infections that affect humans in endemic regions of Europe and Asia. Neurons are the primary target for TBEV infection in the central nervous system. However, knowledge about this viral infection and virus-induced neuronal injury is fragmental. Here, we directly examined the pathology that occurs after TBEV infection in human primary neurons. We exploited the advantages of advanced high-pressure freezing and free ...[more]

PMID: 26073783

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Project description:PurposeTick-Borne Encephalitis (TBE), a disease caused by Tick-Borne Encephalitis Virus (TBEV), is emerging in Italy. This study aimed to characterize the epidemiological, clinical, laboratory, imaging and electroencephalogram characteristics in Belluno, North-East Italy.Results76% were males, mean age 53 years; 50% did not report tick bite. 72% had a biphasic course, 42% a monophasic one, 8 cases of abortive TBE. Mostly no specific symptoms were observed, together with neurological signs and symptoms. None died, but 35% had sequelae at the one-month follow-up. Men had a higher risk of having neurological/neurocognitive sequelae; paresthesia or tremors were associated independently with sequelae. In terms of laboratory data, thrombocytopenia, neutropenia and lymphocytosis were associated with the first phase (p < .01), while monocytosis, lymphocytopenia, high levels of ESR and CRP with the second (p < .05). Other abnormal laboratory data were observed: high levels of transaminases, bilirubin, GGT, fibrinogen, amylase, LDH, CPK and electrolyte disorders. Most of the liquor showed pleocytosis and increased protein levels. No specific findings characterized imaging; electroencephalogram mainly reported general and focal anomalies in the temporal lobe.ConclusionsAlthough patients have not reported a tick bite, TBEV infection should be considered for diagnosis. Usually no specific symptoms are reported along with neurological signs and symptoms. The biphasic course is more often described than the monophasic course; abortive TBE is sometimes present. Paresthesia and tremors are independently associated with neurological/neurocognitive sequelae; men have a higher risk of having sequelae. The first phase is probably associated with thrombocytopenia, neutropenia and lymphocytosis; the second with monocytosis, lymphocytopenia, high levels of CRP and ESR. Electrolyte disorders, high levels of transaminases, GGT, bilirubin, CPK, LDH, fibrinogen and amylase may characterize TBEV infection.

Dataset Information

Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons.

Publications

Electron Tomography Analysis of Tick-Borne Encephalitis Virus Infection in Human Neurons.

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