丙型肝炎病毒核心蛋白通過在共感染期間通過 Siah-1 介導的蛋

StephenW

丙型肝炎病毒核心蛋白通過在共感染期間通過 Siah-1 介導的蛋白酶體降解下調 HBx 水平來抑制乙型肝炎病毒複製
Sujeong Lee 1 , Hyunyoung Yoon 1 , Jiwoo Han 1 , Kyung Lib Jang 1 2 3
隸屬關係
隸屬關係

    1
    釜山國立大學研究生院綜合生物科學系，釜山 46241，韓國。
    2
    釜山國立大學自然科學學院微生物學系，釜山 46241，韓國。
    3
    釜山國立大學微生物資源研究所，釜山 46241，韓國。

    PMID：34882535 DOI：10.1099/jgv.0.001701

抽象的

大多數臨床和實驗研究表明，在共感染期間丙型肝炎病毒 (HCV) 比乙型肝炎病毒 (HBV) 佔優勢，但機制尚不清楚。在這裡，我們發現 HCV 核心蛋白通過在人肝癌細胞共感染期間下調 HBx 水平來抑制 HBV 複製。為此，HCV 核心蛋白增加了線粒體中的活性氧水平，並激活了細胞核中的共濟失調毛細血管擴張突變檢查點激酶兩條途徑，導致 p53 水平上調。因此，HCV 核心蛋白在缺席同源物 one 表達中誘導 p53 依賴性激活，即 HBx 的 E3 連接酶，導致 HBx 的泛素化和蛋白酶體降解。 HCV 核心蛋白對 HBx 水平的影響在 1.2 聚體 HBV 複製子和體外 HBV 感染系統中均得到準確再現，為 HCV 核心蛋白抑制 HBV 複製提供了證據。本研究可能提供對 HBV 和 HCV 合併感染患者中 HCV 優勢機制的見解。

關鍵詞：核心； HBx;乙型肝炎病毒;丙型肝炎病毒； p53;七缺席同源物1。

StephenW

Hepatitis C virus core protein inhibits hepatitis B virus replication by downregulating HBx levels via Siah-1-mediated proteasomal degradation during coinfection
Sujeong Lee  1 , Hyunyoung Yoon  1 , Jiwoo Han  1 , Kyung Lib Jang  1   2   3
Affiliations
Affiliations

    1
    Department of Integrated Biological Science, The Graduate School, Pusan National University, Busan 46241, Republic of Korea.
    2
    Department of Microbiology, College of Natural Science, Pusan National University, Busan 46241, Republic of Korea.
    3
    Microbiological Resource Research Institute, Pusan National University, Busan 46241, Republic of Korea.

    PMID: 34882535 DOI: 10.1099/jgv.0.001701

Abstract

Most clinical and experimental studies have suggested that hepatitis C virus (HCV) is dominant over hepatitis B virus (HBV) during coinfection, although the mechanism remains unclear. Here, we found that HCV core protein inhibits HBV replication by downregulating HBx levels during coinfection in human hepatoma cells. For this effect, HCV core protein increased reactive oxygen species levels in the mitochondria and activated the ataxia telangiectasia mutated-checkpoint kinase two pathway in the nucleus, resulting in an upregulation of p53 levels. Accordingly, HCV core protein induced p53-dependent activation of seven in absentia homolog one expression, an E3 ligase of HBx, resulting in the ubiquitination and proteasomal degradation of HBx. The effect of the HCV core protein on HBx levels was accurately reproduced in both a 1.2-mer HBV replicon and in vitro HBV infection systems, providing evidence for the inhibition of HBV replication by HCV core protein. The present study may provide insights into the mechanism of HCV dominance in HBV- and HCV-coinfected patients.

Keywords: Core; HBx; Hepatitis B virus; hepatitis C virus; p53; seven in absentia homolog 1.