TBEV gE, TBEV NE, TBEV GE, TBEV CE protein

Tick-borne encephalitis (TBE) is a disease caused by the tick-borne encephalitis virus (TBEV), which is mostly found in Europe and Northeast Asia. TBEV is a positive-sense single-stranded RNA (+ssRNA) virus that belongs to the Flavivirus genus of the Flaviviridae family. The TBEV virion measures about 50 nm in diameter and has a spherical envelope shape. Its genome is approximately 11 kilobases long, with a large open reading frame (ORF) and untranslated regions (UTRs) at the 5' and 3' ends. TBEV's key structural proteins are the envelope protein (E protein) and the membrane protein (M protein), with the former playing an important role in viral infection. The E protein is the primary component of the TBEV particle and is separated into four domains. Domain I is the core of the E protein, forming a β-barrel structure. Domain II is involved in dimer interface formation and contains glycosylation sites. Domain III has an immunoglobulin-like fold, possibly related to binding to host receptors. Domain IV is associated with the transmembrane region and membrane-binding portion. The M protein is smaller and is primarily responsible for stabilizing the E protein's shape, as well as for viral particle maturation. TBEV has three subtypes: European (TBEV-Eu), Siberian (TBEV-Sib), and Far Eastern (TBEV-FE). Each subtype differs in geographic distribution and pathogenicity. In addition to these three main subtypes, the Baikalian subtype (TBEV-Bkl) and Himalayan subtype (TBEV-Him) have recently been identified. These subtypes exhibit some differences in epidemiological and pathological characteristics.

Figure 1. Structure of the TBEV E Protein (A: Side View of a Single TBEV E Protein Monomer B: Top View of the Soluble TBEV E Protein Dimer) (Source: Kubinski M, et al., 2020)

The assembly of TBEV is complicated, taking place predominantly in the host cell's endoplasmic reticulum (ER) and Golgi network. Virion synthesis occurs in stages: initially, viral proteins are generated in the rough ER, followed by the capture of genomic RNA within the ER membrane, resulting in nucleocapsid complexes. Mature virions gain structural proteins and lipid envelopes by budding into the ER lumen. In the Golgi apparatus, immature virions mature in an acidic environment. During this step, the M protein separates from its precursor, prM, and the E and M proteins combine to create the final envelope protein complex. Mature TBEV particles are finally discharged from the host cell, triggering a fresh cycle of infection. Mature particles can efficiently infect new cells, whereas immature particles lose infectivity due to structural incompleteness.

TBEV is predominantly transmitted by the bites of infected ticks, with Ixodes ricinus serving as the primary vector in Europe and other hard ticks in Siberia and the Far East. In addition to tick transmission, TBEV can be spread through the eating of unpasteurized dairy products from infected animals. During the viremic phase in infected animals, the virus can be released at low levels into milk, facilitating transmission to humans via unpasteurized dairy products. TBE manifests clinically as fever, meningitis, encephalitis, and, in severe cases, long-term neurological problems or death. The symptoms and course of the disease differ depending on the viral subtype, with the TBEV-FE subtype being associated with the most severe form of the sickness, whilst people infected with the TBEV-Eu subtype had milder symptoms and a lower fatality rate. The overall mortality rate for TBE is between 0.5% and 2%. Vaccination is currently the primary method for preventing and controlling TBE. Several effective vaccines are available to prevent TBE, however low immunization coverage remains a significant issue. Vaccine promotion is influenced by several factors, including public knowledge of vaccination, vaccine availability, and vaccination rates in high-risk populations. Furthermore, global climate change may alter tick distribution ranges, thus raising the risk of TBE. To summarize, while immunization is an effective preventive intervention, the incidence of TBE is increasing due to changes in tick habitats and poor vaccine coverage. Future efforts are required to develop particular antiviral medications against TBEV and to promote immunization to address the developing challenges in prevention and control.

Recombinant Tick-Borne Encephalitis Virus Glycoprotein E
Recombinant TBE Virus Envelope Glycoprotein E
TBEV gE Recombinant Protein