Tick-borne encephalitis virus: molecular determinants of neuropathogenesis of an emerging pathogen

Tick-borne encephalitis virus (TBEV) is a zoonotic agent causing severe encephalitis. The transmission cycle involves the virus, the Ixodes tick vector, and a vertebrate reservoir, such as small mammals (rodents, or shrews). Humans are accidentally involved in this transmission cycle. Tick-borne encephalitis (TBE) has been a growing public health problem in Europe and Asia over the past 30 years. The mechanisms involved in the development of TBE are very complex and likely multifactorial, involving both host and viral factors. The purpose of this review is to provide an overview of the current literature on TBE neuropathogenesis in the human host and to demonstrate the emergence of common themes in the molecular pathogenesis of TBE in humans. We discuss and review data on experimental study models and on both viral (molecular genetics of TBEV) and host (immune response, and genetic background) factors involved in TBE neuropathogenesis in the context of human infection.