Unraveling the Role of Human Microglia in Tick-Borne Encephalitis Virus Infection: Insights into Neuroinflammation and Viral Pathogenesis.

Tick-borne encephalitis virus (TBEV) is a neurotropic orthoflavivirus responsible for severe infections of the central nervous system. Although neurons are predominantly targeted, specific involvement of microglia in pathogenesis of TBE is not yet fully understood. In this study, the susceptibility of human microglia to TBEV is investigated, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. In particular, immune response varied significantly with the viral strain, as shown by the differential secretion of cytokines and chemokines such as IP-10, MCP-1, IL-8 and IL-6, quantified using a Luminex 48-plex assay. The most virulent strain triggered the highest cytokine induction. Electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology and contribute to a deeper understanding of TBE pathogenesis and neuroinflammation.

Frequency of Leiden Mutation in Newborns with Birth Weight below 1500 g.

It has been hypothesized that fetal prematurity or Intrauterine Growth Restriction (IUGR) could be related to the presence of factor V of Leiden mutation. This mutation is associated with a higher incidence of pregnancy difficulties that can result in preterm birth. The frequency of Leiden mutation was investigated in the group of newborns with a low birth weight below 1500 g over a six-year period from 2015 to 2020. During this period, 339 newborns were tested, of which 42 newborns with V Leiden mutation (12.4%) were detected. The average of its occurrence frequency in the Czech population was determined as 5.0% based on published studies. In our research, the occurrence of the V Leiden mutation was found significantly higher in newborns under 1500 g. At the same time, we did not demonstrate an increased frequency of births at lower gestational weeks, lower birth weight, or an association with sex in newborns with a positive diagnosis of the Leiden V factor.