A new class of receptor for herpes simplex virus has heptad repeat motifs that are common to membrane fusion proteins
A new class of receptor for herpes simplex virus has heptad repeat motifs that are common to membrane fusion proteins
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DOI：
10.1128/jvi.79.12.7419-7430.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Fuller, AO
中科院分区：
文献类型：
--
作者：
Perez, A;Li, QX;Fuller, AO
我们通过表达克隆分离出一种人cDNA，并将其基因产物鉴定为一种新的人蛋白质，它能使单纯疱疹病毒（HSV）进入细胞并感染细胞。该基因被命名为hfl - B5，编码一种II型细胞表面膜蛋白B5，它在人原代组织和细胞系中广泛表达。它在细胞外C末端包含一个高分值的七肽重复序列，预计会像细胞中的SNARE蛋白或一些病毒融合蛋白那样形成一个用于卷曲螺旋的α - 螺旋。一种与七肽重复α - 螺旋具有相同序列的合成的30聚体肽可阻断HSV对表达B5的猪细胞和人HEp - 2细胞的感染。人B5在HEp - 2细胞中的瞬时表达即使在没有病毒蛋白的情况下也会导致多核细胞形成增加。B5蛋白满足作为HSV进入的受体或辅助受体的所有标准。HSV利用一种含假定膜融合结构域的人细胞受体（如B5），这提供了一个例子，即一种具有广泛嗜性的致病病毒篡夺了一种广泛表达的细胞蛋白，使其在导致膜融合的感染事件中发挥作用。
We isolated a human cDNA by expression cloning and characterized its gene product as a new human protein that enables entry and infection of herpes simplex virus (HSV). The gene, designated hfl-B5, encodes a type II cell surface membrane protein, B5, that is broadly expressed in human primary tissue and cell lines. It contains a high-scoring heptad repeat at the extracellular C terminus that is predicted to form an alpha-helix for coiled coils like those in cellular SNAREs or in some viral fusion proteins. A synthetic 30-mer peptide that has the same sequence as the heptad repeat alpha-helix blocks HSV infection of B5-expressing porcine cells and human HEp-2 cells. Transient expression of human B5 in HEp-2 cells results in increased polykarocyte formation even in the absence of viral proteins. The B5 protein fulfills all criteria as a receptor or coreceptor for HSV entry. Use by HSV of a human cellular receptor, such as B5, that contains putative membrane fusion domains provides an example where a pathogenic virus with broad tropism has usurped a widely expressed cellular protein to function in infection at events that lead to membrane fusion.