Viroporin potential of the lentivirus lytic peptide (LLP) domains of the HIV-1 gp41 protein
Viroporin potential of the lentivirus lytic peptide (LLP) domains of the HIV-1 gp41 protein
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DOI：
10.1186/1743-422x-4-123
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发表时间：
2007-11-20
期刊：
影响因子：
4.8
通讯作者：
Wimley, William C.
中科院分区：
文献类型：
--
作者：
Costin, Joshua M.;Rausch, Joshua M.;Wimley, William C.
背景资料：HIV-1介导感染者CD 4+细胞水平降低的机制正在被深入研究，这对艾滋病药物和疫苗的开发具有广泛的意义。许多科的裂解性病毒引起的细胞膜离子渗透性的病毒诱导的变化有助于细胞病变。HIV-1诱导质膜离子转运紊乱。TM（gp 41）的羧基末端含有潜在的两亲性α-螺旋基序，其通过与天然存在的溶细胞肽的结构相似性来鉴定。这些序列被命名为慢病毒裂解肽（LLP）-1、-2和-3。结果：对应于LLP结构域的肽（来自进化枝B病毒）分配到脂膜中，折叠成α-螺旋并破坏模型膜通透性。LLP-1 D的进化枝D HIV-1病毒的LLP-1结构域对应的肽，LLP-1D表现出类似的活性的进化枝B病毒的LLP-1结构域在所有的assays，尽管缺乏氨基酸序列identity.Conclusion：这些结果表明，C-末端结构域的HIV-1 Env蛋白可能形成一个离子通道，或viroporin。对LLP结构域的功能及其在病毒复制周期中的作用的进一步了解可能有助于开发新型HIV药物。
Background: Mechanisms by which HIV-1 mediates reductions in CD4+ cell levels in infected persons are being intensely investigated, and have broad implications for AIDS drug and vaccine development. Virally induced changes in membrane ionic permeability induced by lytic viruses of many families contribute to cytopathogenesis. HIV-1 induces disturbances in plasma membrane ion transport. The carboxyl terminus of TM (gp41) contains potential amphipathic alpha-helical motifs identified through their structural similarities to naturally occurring cytolytic peptides. These sequences have been dubbed lentiviral lytic peptides (LLP) -1, -2, and -3.Results: Peptides corresponding to the LLP domains (from a clade B virus) partition into lipid membranes, fold into a-helices and disrupt model membrane permeability. A peptide corresponding to the LLP-1 domain of a clade D HIV-1 virus, LLP-1D displayed similar activity to the LLP-1 domain of the clade B virus in all assays, despite a lack of amino acid sequence identity.Conclusion: These results suggest that the C-terminal domains of HIV-1 Env proteins may form an ion channel, or viroporin. Increased understanding of the function of LLP domains and their role in the viral replication cycle could allow for the development of novel HIV drugs.