Regulation of HBV precore protein maturation is driven by its signal peptide sequence

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F24%3A00604145" target="_blank" >RIV/61388963:_____/24:00604145 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Regulation of HBV precore protein maturation is driven by its signal peptide sequence

Original language description

The hepatitis B virus (HBV) can induce both acute and chronic hepatitis and is a major global health problem. HBV is a small enveloped DNA virus with a genome containing only four open reading frames, which largely overlap and encode multiple proteins using different in-frame start codons. For example, the HBV preC-C gene gives rise to two distinct products that are translated from different mRNAs –core protein (HBc) and precore protein (HBe). HBc is a cytosolic protein responsible for the assembly of icosahedral viral particles and encapsidation of pre-genomic RNA. On the other hand, the HBe precursor (p25) is directed to the endoplasmic reticulum (ER) where cleavage of the signal peptide (sp) yields the first processing product, p22. The majority of p22 is further processed at its C-terminus by furin protease in the trans-Golgi network, giving rise to mature HBe antigen (p17). The mature protein is secreted and performs an immunomodulatory function in establishing a persistent infection. However, approximately 15 20% of p22 does not enter the secretory pathway and is retrotranslocated back into the cytosol and transported to the nucleus. The biological function of the intracellular precore protein pool remains poorly understood and the mechanism by which p22 is distributed to different cellular compartments is unclear. We have described that the translocation of the precore precursor p25 to the ER is promoted by the translocon-associated protein complex (TRAP). Within the p25 sp sequence we have identified three cysteine residues that control the efficiency of sp cleavage and appear to act as an auto-regulatory factor that influencing the intracellular localisation of the precore. In ongoing experiments, we also investigate the contribution of individual HBV precore protein constructs to the activation of unfolded protein response.n

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/LX22NPO5103" target="_blank" >LX22NPO5103: National Institute of Virology and Bacteriology</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů