Tick-borne encephalitis (TBE), which is attributed to the tick-borne encephalitis virus (TBEV), exhibits a prevalent occurrence in forest regions across Europe and Asia. Globally, over 10, 000 cases of TBE are reported annually, yet the morality rate remains relatively low [1]. Patients diagnosed with TBE typically receive moderate care, including temperature reduction and antiviral treatment. Thus far, TBE vaccines represent the sole efficacious measure for preventing TBE [2]. Instances of vaccine failure, although rare, have been associated with host and virus factors. Regrettably, the progress in developing vaccines for TBE has reached an impasse. Based on the diagnostic criteria for occupational forest encephalitis, TBEV infection can be categorized into two stages: an initial phase characterized by sudden-onset fever, accompanied by nausea, fatigue, headache, joint pain, and others, followed by central nervous system symptoms of varying in 20–30% of patients. Alimentary infections caused by encephalitis viruses have been linked to recent rise in TBEV cases in Europe, with the consumption of raw milk from cows, goats, and sheep being a contributing factor [3]. Although the case-fatality rate of TBEV is estimated to be between 0 and 1.4%, damage to the central nervous system can persist [4,5]. The occurrence of TBE is typically observed in in forested regions. However, due to the ongoing development in western China and the revitalization of northeastern China through ecological tourism, tick activity has escalated, leading to the spread of TBE infection to urban areas. In the field of research, proteomics and metabolomics techniques have proven valuable in establishing the associations between metabolites and proteins with the onset and progression of disease [6]. Consequently, these methodologies have been successfully employed in the study of viral infections and communicable diseases [[7], [8], [9]].

Our team has previously completed a systematic analysis of serum metabolites in a specific group of adult patients with TBE [10]. However, it is important to note that interpreting data from a single type of study can be challenging due to the intricate biochemical regulation occurring at various levels. To address this limitation, our current study aimed to evaluate TBE-related molecular changes by conducting proteomic and metabolomic analyses on serum samples obtained from healthy subjects and TBE patients.

The objective of this study is to expand our understanding of the molecular mechanisms underlying TBE in patients. To achieve this, we utilized isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic and liquid chromatography-mass spectrometry-based metabolomic techniques to obtain unbiased profiling data. Additionally, we employed Integrated Molecular pathway analysis to conduct integrated molecular pathway and network analyses. The findings from this study will contribute to a more comprehensive comprehension of the pathogenesis of TBE.