Nejvíce citovaný článek - PubMed ID 28432926
Tick-borne encephalitis virus infects human brain microvascular endothelial cells without compromising blood-brain barrier integrity
Tick-borne encephalitis virus (TBEV) targets the central nervous system (CNS), leading to potentially severe neurological complications. The neurovascular unit plays a fundamental role in the CNS and in the neuroinvasion of TBEV. However, the role of human brain pericytes, a key component of the neurovascular unit, during TBEV infection has not yet been elucidated. In this study, TBEV infection of the primary human brain perivascular pericytes was investigated with highly virulent Hypr strain and mildly virulent Neudoerfl strain. We used Luminex assay to measure cytokines/chemokines and growth factors. Both viral strains showed comparable replication kinetics, peaking at 3 days post infection (dpi). Intracellular viral RNA copies peaked at 6 dpi for Hypr and 3 dpi for Neudoerfl cultures. According to immunofluorescence staining, only small proportion of pericytes were infected (3% for Hypr and 2% for Neudoerfl), and no cytopathic effect was observed in the infected cells. In cell culture supernatants, IL-6 production was detected at 3 dpi, together with slight increases in IL-15 and IL-4, but IP-10, RANTES and MCP-1 were the main chemokines released after TBEV infection. These chemokines play key roles in both immune defense and immunopathology during TBE. This study suggests that pericytes are an important source of these signaling molecules during TBEV infection in the brain.
- Klíčová slova
- CCL5, CXCL10, chemokine, flavivirus, human pericytes, infection, inflammation, tick-borne encephalitis virus,
- MeSH
- chemokin CCL5 * metabolismus MeSH
- chemokin CXCL10 * metabolismus MeSH
- cytokiny metabolismus MeSH
- klíšťová encefalitida * virologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mozek * virologie metabolismus patologie MeSH
- pericyty * virologie metabolismus MeSH
- replikace viru MeSH
- viry klíšťové encefalitidy * fyziologie patogenita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- CCL5 protein, human MeSH Prohlížeč
- chemokin CCL5 * MeSH
- chemokin CXCL10 * MeSH
- CXCL10 protein, human MeSH Prohlížeč
- cytokiny MeSH
Matrix metalloproteinases (MMPs) play an important role in central nervous system infections. We analysed the levels of 8 different MMPs in the cerebrospinal fluid (CSF) of 89 adult patients infected with tick-borne encephalitis (TBE) virus and compared them with the levels in a control group. MMP-9 was the only MMP that showed significantly increased CSF levels in TBE patients. Serum MMP-9 levels were subsequently measured in 101 adult TBE patients at various time points during the neurological phase of TBE and at follow-up. In addition, serum MMP-9 was analysed in 37 paediatric TBE patients. Compared with control levels, both paediatric and adult TBE patients had significantly elevated serum MMP-9 levels. In most adult patients, serum MMP-9 levels peaked at hospital admission, with higher serum MMP-9 levels observed in patients with encephalitis than in patients with meningitis. Elevated serum MMP-9 levels were observed throughout hospitalisation but decreased to normal levels at follow-up. Serum MMP-9 levels correlated with clinical course, especially in patients heterozygous for the single-nucleotide polymorphism rs17576 (A/G; Gln279Arg) in the MMP9 gene. The results highlight the importance of MMP-9 in the pathogenesis of TBE and suggest that serum MMP-9 may serve as a promising bioindicator of TBE in both paediatric and adult TBE patients.
- Klíčová slova
- Cerebrospinal fluid, Matrix matalloproteinase, Neuroinfection, Tick-borne encephalitis,
- MeSH
- biologické markery MeSH
- dítě MeSH
- dospělí MeSH
- jednonukleotidový polymorfismus MeSH
- klíšťová encefalitida * diagnóza mozkomíšní mok MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 genetika MeSH
- viry klíšťové encefalitidy * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- matrixová metaloproteinasa 9 MeSH
- MMP9 protein, human MeSH Prohlížeč
The aim of this review is to follow the history of studies on endemiv arboviruses and the diseases they cause which were detected in the Czech lands (Bohemia, Moravia and Silesia (i.e., the Czech Republic)). The viruses involve tick-borne encephalitis, West Nile and Usutu flaviviruses; the Sindbis alphavirus; Ťahyňa, Batai, Lednice and Sedlec bunyaviruses; the Uukuniemi phlebovirus; and the Tribeč orbivirus. Arboviruses temporarily imported from abroad to the Czech Republic have been omitted. This brief historical review includes a bibliography of all relevant papers.
- Klíčová slova
- arthropods, birds, mammals, mosquitoes, ticks,
- MeSH
- arbovirové infekce dějiny MeSH
- arboviry fyziologie MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
Dogs are frequently infected with the tick-borne encephalitis virus (TBEV). However, to date, only a few clinically manifest cases of tick-borne encephalitis (TBE) have been reported in dogs. In this study, three-month-old beagle dogs were infected with TBEV through a subcutaneous injection. Body temperature, clinical signs, blood haematology, blood biochemistry, and immune responses were monitored for up to 28 days postinfection (p.i.). No changes in body temperature or clinical signs were observed in the infected dogs. Most haematology and blood biochemistry parameters were unchanged after the infection, except for a slight reduction in blood lymphocyte counts, but they were within the physiological range. Low-titre viraemia was detected in 2/4 infected dogs between days 1 and 3 p.i. All infected dogs developed a robust immune response, in terms of neutralising antibodies. Thus, TBEV infections lead to effective seroconversion in dogs. Next, to assess TBEV exposure in dogs in the TBEV-endemic region of the Czech Republic, we conducted a serosurvey. Virus neutralisation tests revealed TBEV-specific antibodies in 17 of 130 (13.07%) healthy dogs, which confirmed a high, but clinically inappreciable TBEV exposure rate in the endemic area. The seropositivity rate was similar (12.7%; 41 positives out of 323) in a subgroup of dogs with various clinical disorders, and it was 13.4% (23 out of 171) in a subgroup of dogs with signs of acute neurological disease. Two dogs with fatal acute meningoencephalitis showed positive results for TBEV-specific IgM and IgG antibodies. These data extended our understanding of the clinical presentation of TBEV infections.
- Klíčová slova
- dogs, experimental infection, seroprevalence, tick-borne encephalitis,
- MeSH
- imunoglobulin G krev MeSH
- imunoglobulin M krev MeSH
- klíšťová encefalitida diagnóza imunologie veterinární virologie MeSH
- modely nemocí na zvířatech MeSH
- nemoci psů diagnóza imunologie virologie MeSH
- neutralizační testy MeSH
- protilátky virové krev MeSH
- psi MeSH
- virové zoonózy diagnóza imunologie virologie MeSH
- viry klíšťové encefalitidy * MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- imunoglobulin G MeSH
- imunoglobulin M MeSH
- protilátky virové MeSH