The role of low pH and disulfide shuffling in the entry and fusion of Semliki Forest virus and Sindbis virus
The role of low pH and disulfide shuffling in the entry and fusion of Semliki Forest virus and Sindbis virus
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DOI：
10.1006/viro.1998.9275
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发表时间：
1998-09-01
期刊：
影响因子：
3.7
通讯作者：
Kielian, M
中科院分区：
文献类型：
--
作者：
Glomb-Reinmund, S;Kielian, M
塞姆利基森林病毒（Semliki Forest Virus，SFV）是一种包膜甲病毒，通过内吞囊泡中的低pH诱导的膜融合反应感染细胞。低pH在甲病毒属辛德毕斯病毒（SIN）进入中的作用尚不清楚，已经提出了一种涉及中性pH下受体诱导的二硫键重排的替代融合机制。本文用弱碱性NH_4Cl或液泡ATP酶抑制剂巴弗洛霉素A-1或康卡那霉素中和内体pH，平行比较了SFV和SIN的进入特性。（2-硝基苯甲酸）（DTNB）、对氯汞苯磺酸（pCMBS）和一溴三甲基氨二亚胺（Thiolyte Ma）用于抑制硫醇-二硫化物交换反应。用NH_4Cl、巴弗洛霉素或康卡那霉素中和内体pH可抑制SN和SIN的初次感染。抑制所需的NH_4Cl或巴弗洛霉素浓度与SFV SIN和SFV的pH移位突变体的膜融合的pH依赖性相关。SN和SIN感染被巯基阻断剂DTNB部分抑制，但不被pCMBS或Thiolyte MQ抑制。我们的数据表明，酸性内体pH诱导SFV和SIN在病毒感染过程中的融合活性。(C)北京：科学出版社.
Semliki Forest Virus (SFV), an enveloped alphavirus, infects cells via a membrane fusion reaction that is induced by the low pH in endocytic vesicles. The role of low pH in the entry of the alphavirus Sindbis virus (SIN) is unclear, and an alternative fusion mechanism involving receptor-induced disulfide bond rearrangements at neutral pH has been proposed. The entry properties of SFV and SIN were here compared in parallel using treatment with the weak base NH4Cl or the vacuolar ATPase inhibitors bafilomycin A-1 or concanamycin to neutralize endosome pH, Three membrane impermeant thiol modifying reagents, 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB), p-chloromercuriphenylsulfonic acid (pCMBS), and monobromotrimethylammoniobimane (Thiolyte Ma), were used to inhibit thiol-disulfide exchange reactions. Primary infection by both SN and SIN was inhibited by neutralization of endosome pH using NH4Cl, bafilomycin, or concanamycin, The concentration of NH4Cl or bafilomycin required for inhibition correlated with the pH dependence of membrane fusion for SFV SIN, and a pH-shift mutant of SFV. SN and SIN infection were partially inhibited by the thiol blocker DTNB, but not by pCMBS or Thiolyte MQ. Our data suggest that acidic endosomal pH induces the fusion activity of both SFV and SIN during Virus infection. (C) 1998 Academic Press.