Title:Új ismeretek a veszettség kórfejlődéséről és immunológiájáról - Irodalmi összefoglaló
SUMMARY Rabies virus (RABV) is a neurotropic, zoonotic virus that causes rabies encephali-tis. Rabies leads to the death of more than 50,000 individuals worldwide, annu-ally. The pathogenesis of rabies is unique: the virus enters the muscles through bites of rabid animals, which is followed by the invasion of peripheral nerves and axonal spread to the central nervous system (CNS). In later stages of infec-tion, the virus spreads centrifugally to the salivary glands and other peripheral organs. RABV virions attach to different cell membrane receptors (nAChR, NCAM, p75NTR) and enter the host cells via pinocytosis. The ribonucleoprotein complex with the structural RNA-dependent RNA polymerase enzyme is responsible for transcription and replication. The five viral proteins are produced in a concentra-tion gradient and the accumulation of N and M proteins is associated with the switch of the polymerase enzyme from transcription to replication. The assem-bly of new virions takes place near the budding sites, where the glycoproteins are integrated in the cell membrane. While attenuated strains trigger the acti-vation of various innate and adaptive immune responses, wild-type RABV suc-cessfully evades the host immunity. The production and effect of interferons are inhibited at multiple key steps; the modified function of dendritic cells favours viral spreading to the CNS; certain pro-inflammatory pathways are down-regu-lated (which interferes with lymphocyte chemotaxis and blood-brain barrier per-meability); apoptosis of infected neurons is prevented, but apoptosis of immune effector cells is induced. Main factors in survival of rabies encephalitis include the rapid induction of the innate immune system at the periphery; the increase in blood-brain barrier permeability; the induction of a strong T-helper 1-biased immune response in the CNS followed by a sufficient production of virus neu-tralizing antibodies by invading B cells; and the optimal regulation of the deli-cate balance between pro- and anti-inflammatory cascades in the brain.