Tick-borne encephalitis - Causes and pathogenesis

Causes of tick-borne encephalitis

Tick-borne encephalitis is caused by the tick-borne encephalitis virus, which belongs to the Flaviviridae family. The virus is 45-50 nm in size and consists of a nucleocapsid with a cubic type of symmetry and is covered with a membrane. The nucleocapsid contains RNA and protein C (core). The membrane consists of two glycoproteins (membrane M, envelope E) and lipids. Based on the homology analysis of the gene fragment encoding protein E, five main genotypes of the virus are distinguished:

• genotype 1 - Far Eastern variant;
• genotype 2 - Western (Central European) variant;
• genotype 3 - Greco-Turkish variant;
• genotype 4 - East Siberian variant;
• genotype 5 - Ural-Siberian variant.

Genotype 5 is the most common, found in most of the tick-borne encephalitis virus range.

Tick-borne encephalitis virus is cultivated in chicken embryos and tissue cultures of various origins. With prolonged passaging, the pathogenicity of the virus decreases. Among laboratory animals, white mice, rat sucklings, hamsters and monkeys are most susceptible to infection with the virus, and among domestic animals - sheep, goats, pigs and horses. The virus has varying degrees of resistance to various environmental factors: it dies within 2-3 minutes when boiled, is easily destroyed by pasteurization, treatment with solvents and disinfectants, but is able to remain viable for a long time at low temperatures and in a dried state. The virus persists for quite a long time in food products such as milk or butter, which can sometimes be sources of infection. The virus is resistant to low concentrations of hydrochloric acid, so foodborne infection is possible.

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Pathogenesis of tick-borne encephalitis

After penetration, the virus locally replicates in skin cells. Degenerative-inflammatory changes develop in the tissues at the site of the bite. In the case of alimentary infection, the virus is fixed in the epithelial cells of the gastrointestinal tract.

The first wave of viremia (transient) is caused by the penetration of the virus into the blood from the sites of primary localization. At the end of the incubation period, the second wave of viremia occurs, coinciding in time with the beginning of the virus reproduction in the internal organs. The final phase is the introduction and replication of the virus in the cells of the central nervous system and the peripheral nervous system.

The “plus-strand” RNA of the tick-borne encephalitis virus is capable of directly transmitting genetic information to the ribosomes of a sensitive cell, i.e. performing the functions of mRNA.

Tick-borne encephalitis virus primarily affects the gray matter of the CNS, resulting in polioencephalitis. The lesions observed are nonspecific and include cellular inflammation, hyperplasia, glial proliferation, and neuronal necrosis.

Progressive forms of tick-borne encephalitis are associated with long-term preservation of the virus in an active form in the cells of the central nervous system. Mutant forms of the virus play a significant role in the development of persistent infection.

Pathomorphology of tick-borne encephalitis

Microscopy of the brain and membranes reveals hyperemia and edema, infiltrates of mono- and polynuclear cells, mesodermal and glial reactions. Inflammatory and degenerative changes in neurons are localized mainly in the anterior horns of the cervical segments of the spinal cord, nuclei of the medulla oblongata, pons, and cerebral cortex. Destructive vasculitis with necrotic foci and point hemorrhages is characteristic. Fibrous changes in the membranes of the brain with the formation of adhesions and arachnoid cysts, and pronounced proliferation of glia are typical for the chronic stage of tick-borne encephalitis. The most severe, irreversible lesions occur in the cells of the anterior horns of the cervical segments of the spinal cord.