Hepatitis B virus is a stealth virus that minimizes proteomic and secretomic changes in primary human hepatocytes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00641862" target="_blank" >RIV/61388963:_____/25:00641862 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1099/jgv.0.002170" target="_blank" >https://doi.org/10.1099/jgv.0.002170</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1099/jgv.0.002170" target="_blank" >10.1099/jgv.0.002170</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hepatitis B virus is a stealth virus that minimizes proteomic and secretomic changes in primary human hepatocytes

Popis výsledku v původním jazyce

Hepatitis B virus (HBV) is a hepatotropic DNA virus that infects over 250 million people worldwide and causes serious liver diseases. HBV infection can modulate host cellular processes, potentially inducing proteomic changes in hepatocytes. In this study, we investigated how acute HBV infection alters the proteome and secretome of primary human hepatocytes, a physiologically relevant in vitro model that retains essential liver-specific functions. Protein-level changes in cell lysates and culture supernatants were quantified 8 days post-infection using data-independent acquisition MS. We used HBV infection in the presence of the entry inhibitor bulevirtide as a control to separate the effects of productive infection from those caused by inoculum-associated components. Despite robust infection, active HBV replication induced only subtle changes in host protein levels. Orthogonal validation of MS-identified candidates confirmed reticulocalbin-2 as a novel host factor downregulated during productive HBV infection. The functional role of candidate proteins identified by MS was assessed in vitro by siRNA-mediated knockdown and measurement of viral replication markers. Knockdown had no impact on viral RNA or antigen levels, suggesting that the observed proteomic changes may reflect stress responses or broader modulation of the hepatic microenvironment. Our findings support the concept of HBV as a stealth virus and underscore the importance of carefully controlled experimental systems for studying host responses to infection in vitro.

Název v anglickém jazyce

Hepatitis B virus is a stealth virus that minimizes proteomic and secretomic changes in primary human hepatocytes

Popis výsledku anglicky

Hepatitis B virus (HBV) is a hepatotropic DNA virus that infects over 250 million people worldwide and causes serious liver diseases. HBV infection can modulate host cellular processes, potentially inducing proteomic changes in hepatocytes. In this study, we investigated how acute HBV infection alters the proteome and secretome of primary human hepatocytes, a physiologically relevant in vitro model that retains essential liver-specific functions. Protein-level changes in cell lysates and culture supernatants were quantified 8 days post-infection using data-independent acquisition MS. We used HBV infection in the presence of the entry inhibitor bulevirtide as a control to separate the effects of productive infection from those caused by inoculum-associated components. Despite robust infection, active HBV replication induced only subtle changes in host protein levels. Orthogonal validation of MS-identified candidates confirmed reticulocalbin-2 as a novel host factor downregulated during productive HBV infection. The functional role of candidate proteins identified by MS was assessed in vitro by siRNA-mediated knockdown and measurement of viral replication markers. Knockdown had no impact on viral RNA or antigen levels, suggesting that the observed proteomic changes may reflect stress responses or broader modulation of the hepatic microenvironment. Our findings support the concept of HBV as a stealth virus and underscore the importance of carefully controlled experimental systems for studying host responses to infection in vitro.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10607 - Virology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

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 General Virology

ISSN

0022-1317

e-ISSN

1465-2099

Svazek periodika

106

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

18

Strana od-do

002170

Kód UT WoS článku

001622006800004

EID výsledku v databázi Scopus

2-s2.0-105021075849