TBEV preM
Description
Product Specs
Q&A
Basic Research Questions
What is the structural and functional role of preM in TBEV replication?
TBEV preM (premembrane) protein is a structural component critical for viral assembly and maturation. It forms a heterodimer with the envelope (E) protein, stabilizing the E protein in its immature conformation and preventing premature fusion with host membranes. During viral maturation in the Golgi apparatus, preM is cleaved by furin-like proteases into the mature membrane (M) protein, enabling conformational changes required for infectivity .
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Methodological approach: Structural analysis via cryo-electron microscopy (cryo-EM) and mutagenesis studies to identify cleavage sites and protein-protein interactions .
How does preM contribute to TBEV antigenicity and immune evasion?
preM influences antigenic properties by modulating E protein exposure. Antibody neutralization assays reveal that chimeric viruses with TBEV preM-E proteins (e.g., LGTVT:prME) retain structural authenticity, enabling cross-reactivity with TBEV vaccines (e.g., FSME-IMMUNE®) .
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Methodological approach: Neutralization assays using sera from vaccinated individuals to measure 50% neutralization titers (NT50) and assess cross-reactivity .
What experimental models are used to study preM’s role in neurotropism?
Chimeric flaviviruses (e.g., TBEV prM-E inserted into Langat virus backbone) combined with 3D whole-brain optical projection tomography (OPT) and confocal microscopy reveal that preM-E proteins determine cerebellar tropism. TBEV preferentially infects Purkinje cells, while chimeric viruses show reduced neurovirulence .
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Methodological approach: Intracerebral inoculation in murine models, OPT imaging, and tissue-specific viral load quantification .
Advanced Research Questions
How do preM genetic variations impact TBEV pathogenicity and vaccine efficacy?
Genetic divergence in preM-E proteins (e.g., >10% nucleotide differences) alters viral entry efficiency and immune recognition. For example, chimeric LGTVT:prME exhibits attenuated peripheral replication due to suboptimal interactions between TBEV preM and LGTV capsid proteins .
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Methodological approach: Reverse genetics to generate chimeras, paired with in vivo pathogenesis studies and neutralization escape mutant analysis .
What contradictions exist in preM’s role in immune activation versus evasion?
While preM-E proteins drive neutralizing antibody responses, they also exhibit strain-specific differences in macrophage infection and immune activation. For example, TBEV induces robust type I interferon (IFN-α/β) responses via RIG-I/MDA5 pathways, whereas chimeric viruses show delayed IFN activation .
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Methodological approach: Comparative transcriptomics of infected macrophages and neurons, coupled with IFN receptor knockout models .
How can preM-specific biomarkers improve TBE diagnosis during early infection?
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Methodological approach: Multiplex RT-PCR assays for preM-E RNA in serum/CSF/urine, validated against ELISA-based IgM/IgG detection .
Table 1: Neurotropism Patterns of TBEV vs. Chimeric LGTVT:prME
Table 2: Diagnostic Performance of preM-E Biomarkers
Methodological Recommendations
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For structural studies: Prioritize cryo-EM and glycosylation profiling to resolve preM-E interactions .
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For pathogenesis studies: Use Mavs-/- murine models to isolate structural protein effects from innate immune confounding .
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For diagnostics: Combine serum IgM ELISA with CSF RT-PCR in endemic regions to address false negatives in vaccine breakthrough cases .
Product Science Overview
Tick-borne encephalitis virus (TBEV) is a significant human pathogen belonging to the family Flaviviridae. It is primarily transmitted by ticks and is responsible for causing tick-borne encephalitis (TBE), a severe disease affecting the central nervous system. TBEV is prevalent in Europe and Asia, with up to 15,000 clinical cases reported annually .
The pre-membrane (prM) and envelope (E) proteins of TBEV play crucial roles in the virus’s life cycle and its ability to infect host cells. The prM protein is a precursor to the membrane (M) protein, which, along with the E protein, forms the viral envelope. The E protein is responsible for virus attachment and entry into host cells.
Recombinant TBEV preM involves the expression of the prM and E proteins in a host system, such as mammalian cells, using recombinant DNA technology. This approach allows for the production of subviral particles that mimic the native virus’s structure and antigenic properties. These recombinant subviral particles are valuable for diagnostic purposes and vaccine development .
Recombinant TBEV preM subviral particles have shown promise in diagnostic applications. They can be used to develop enzyme immunoassays (EIAs) for detecting TBEV-specific antibodies in human serum samples. These assays have demonstrated high sensitivity and specificity, making them reliable tools for TBEV serology .
The recombinant Modified Vaccinia virus Ankara (MVA) expressing the prM and E proteins of TBEV (MVA-prME) has been developed as a potential next-generation vaccine. Studies have shown that MVA-prME is highly immunogenic and provides full protection against TBEV infection in animal models. This recombinant vaccine holds promise for improving TBE prevention .
