期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 15, 期 3, 页码 593-606出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2010.3512
关键词
-
资金
- Italian Ministry of Instruction, Universities, and Research [FIRB RBIP067F9E, Reti FIRB RBPR05NWWC_006]
- Italian Ministry of Health-ISS
- Fondazione Roma
Aim: The aim of this study was to determine whether GSH-C4, a hydrophobic glutathione derivative, affects in vitro and in vivo influenza virus infection by interfering with redox-sensitive intracellular pathways involved in the maturation of viral hemagglutinin (HA). Results: GSH-C4 strongly inhibited influenza A virus replication in cultured cells and in lethally infected mice, where it also reduced lung damage and mortality. In cell-culture studies, GSH-C4 arrested viral HA folding; the disulfide-rich glycoprotein remained in the endoplasmic reticulum as a reduced monomer instead of undergoing oligomerization and cell plasma-membrane insertion. HA maturation depends on the host-cell oxidoreductase, protein disulfide isomerase (PDI), whose activity in infected cells is probably facilitated by virus-induced glutathione depletion. By correcting this deficit, GSH-C4 increased levels of reduced PDI and inhibited essential disulfide bond formation in HA. Host-cell glycoprotein expression in uninfected cells was unaffected by glutathione, which thus appears to act exclusively on glutathione-depleted cells. Innovation: All currently approved anti-influenza drugs target essential viral structures, and their efficacy is limited by toxicity and by the almost inevitable selection of drug-resistant viral mutants. GSH-C4 inhibits influenza virus replication by modulating redox-sensitive pathways in infected cells, without producing toxicity in uninfected cells or animals. Novel anti-influenza drugs that target intracellular pathways essential for viral replication (cell-based approach) offer two important potential advantages: they are more difficult for the virus to adapt to and their efficacy should not be dependent on virus type, strain, or antigenic properties. Conclusion: Redox-sensitive host-cell pathways exploited for viral replication are promising targets for effective anti-influenza strategies. Antioxid. Redox Signal. 15, 593-606.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据