UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00640457" target="_blank" >RIV/61388963:_____/25:00640457 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/25:10503868

Výsledek na webu

<a href="https://doi.org/10.1016/j.jbc.2025.110750" target="_blank" >https://doi.org/10.1016/j.jbc.2025.110750</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jbc.2025.110750" target="_blank" >10.1016/j.jbc.2025.110750</a>

Jazyk výsledku

angličtina

Název v původním jazyce

UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress

Popis výsledku v původním jazyce

A critical step in Hepatitis B virus (HBV) maturation and egress is the ubiquitination of the capsid/core protein (HBc), which enables its recognition by the endosomal sorting complex required for transport (ESCRT) machinery and recruitment to multivesicular bodies (MVBs). This study investigates the role of UBE2O, an atypical E2 ubiquitin-conjugating enzyme with intrinsic E3 ligase activity, in nucleocapsid assembly and virion egress. Loss of UBE2O in HBV-infected primary human hepatocytes (PHH) and HepG2-NTCP cells led to a reduction in viral replication, as evidenced by decreased levels of intracellular HBV DNA, pgRNA, capsids, and extracellular HBeAg. Additionally, UBE2O depletion disrupted intracellular nucleocapsid assembly and impaired the secretion of enveloped virions, but the release of naked nucleocapsids remained unaffected. In contrast, UBE2O overexpression enhanced the secretion of mature virions, whereas the expression of its enzymatically inactive mutant inhibited this process. Additionally, UBE2O mediated the monoubiquitination of hypophosphorylated cytoplasmic HBc and capsids. Subcellular localization experiments using confocal microscopy and proximity ligation assays (PLA) demonstrated that UBE2O colocalizes with capsids and ubiquitinated cargo in CD63-positive MVB compartments, indicating its involvement in the endosomal secretory pathway. Collectively, this study identifies UBE2O and its catalytic activity as key regulators of the HBV virion secretion pathway, highlighting its potential as a therapeutic target for HBV treatment.

Název v anglickém jazyce

UBE2O, a host ubiquitin-conjugating enzyme, is a key regulator of hepatitis B virus maturation and egress

Popis výsledku anglicky

A critical step in Hepatitis B virus (HBV) maturation and egress is the ubiquitination of the capsid/core protein (HBc), which enables its recognition by the endosomal sorting complex required for transport (ESCRT) machinery and recruitment to multivesicular bodies (MVBs). This study investigates the role of UBE2O, an atypical E2 ubiquitin-conjugating enzyme with intrinsic E3 ligase activity, in nucleocapsid assembly and virion egress. Loss of UBE2O in HBV-infected primary human hepatocytes (PHH) and HepG2-NTCP cells led to a reduction in viral replication, as evidenced by decreased levels of intracellular HBV DNA, pgRNA, capsids, and extracellular HBeAg. Additionally, UBE2O depletion disrupted intracellular nucleocapsid assembly and impaired the secretion of enveloped virions, but the release of naked nucleocapsids remained unaffected. In contrast, UBE2O overexpression enhanced the secretion of mature virions, whereas the expression of its enzymatically inactive mutant inhibited this process. Additionally, UBE2O mediated the monoubiquitination of hypophosphorylated cytoplasmic HBc and capsids. Subcellular localization experiments using confocal microscopy and proximity ligation assays (PLA) demonstrated that UBE2O colocalizes with capsids and ubiquitinated cargo in CD63-positive MVB compartments, indicating its involvement in the endosomal secretory pathway. Collectively, this study identifies UBE2O and its catalytic activity as key regulators of the HBV virion secretion pathway, highlighting its potential as a therapeutic target for HBV treatment.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Journal of Biological Chemistry

ISSN

0021-9258

e-ISSN

1083-351X

Svazek periodika

301

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

24

Strana od-do

110750

Kód UT WoS článku

001602642200001

EID výsledku v databázi Scopus

2-s2.0-105018857907