Biogenesis of hepatitis B virus e antigen is driven by translocon-associated protein complex and regulated by conserved cysteine residues within its signal peptide sequence
Helena Zábranská 1 , Aleš Zábranský 1 , Barbora Lubyová 1 , Jan Hodek 1 , Alena Křenková 1 , Martin Hubálek 1 , Jan Weber 1 , Iva Pichová 1
Affiliations
Affiliation
1
Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo n. 2, 166 10, Prague, Czech Republic.
PMID: 34839586 DOI: 10.1111/febs.16304
Abstract
Hepatitis B virus (HBV) uses e antigen (HBe), which is dispensable for virus infectivity, to modulate host immune responses and achieve viral persistence in human hepatocytes. The HBe precursor (p25) is directed to the endoplasmic reticulum (ER), where cleavage of the signal peptide (sp) gives rise to the first processing product, p22. P22 can be retro-translocated back to the cytosol or enter the secretory pathway and undergo a second cleavage event, resulting in secreted p17 (HBe). Here, we report that translocation of p25 to the ER is promoted by translocon-associated protein complex (TRAP). We have found that p25 is not completely translocated into the ER; a fraction of p25 is phosphorylated and remains in the cytoplasm and nucleus. Within the p25 sp sequence, we have identified three cysteine residues that control the efficiency of sp cleavage and contribute to proper subcellular distribution of the precore pool.
Keywords: ER translocation; HBV precore protein; HBe; Hepatitis B virus; TRAP complex; cysteine residues; signal peptide.
This article is protected by copyright. All rights reserved. 作者: 乙肝人1949 时间: 2021-11-29 17:32