Neutralizing antibodies against conserved domains of p15E of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation?
Neutralizing antibodies against conserved domains of p15E of porcine endogenous retroviruses: basis for a vaccine for xenotransplantation?
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DOI：
10.1016/s0042-6822(02)00140-x
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发表时间：
2003-03-15
期刊：
影响因子：
3.7
通讯作者：
Denner, J
中科院分区：
文献类型：
--
作者：
Fiebig, U;Stephan, O;Denner, J
猪异种移植可能为同种异体移植供应有限带来的问题提供一个潜在的解决方案。然而，异种移植可能与微生物的传播风险有关，特别是猪内源性逆转录病毒(PERV)的传播，猪内源性逆转录病毒是猪基因组的组成部分，能够在体外感染人类细胞。预防病毒传播的可能策略包括开发PERV基因敲除动物或有效疫苗。对PERV主要结构蛋白制备的抗血清进行筛选时，发现一种针对重组跨膜蛋白p15E胞外区的山羊抗血清能中和PERV的感染性。利用重叠多肽绘制的表位图显示了两个表位：E1(GPQQLEK)和E2(FEGWFN)。这些序列在所有PERV中都是相同的，并且在所有伽马逆转录病毒中高度保守。有趣的是，从艾滋病患者中分离出来的针对HIV-1序列的抗体(Mab4E10，LWNWFN)与E2部分同源或位于E2附近(Ma62F5，ELDKWA)，已知能中和几种HIV-1毒株。这是第一份报告，显示了伽马逆转录病毒特异性中和抗体的表位图，并展示了与艾滋病毒相应表位的相似性。不同逆转录病毒的这些跨膜蛋白结构域是中和抗体的有效靶点，并可能成为研制抗逆转录病毒疫苗的有用抗原。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Porcine xenotransplants may offer a potential solution to the problem posed by the limited supply of allotransplants. However, xenotransplantation may be associated with the risk of transmission of microorganisms, in particular of porcine endogenous retroviruses (PERVs) that are an integral part of the porcine genome and able to infect human cells in vitro. Possible strategies to prevent virus transmission include the development of PERV knockout animals or of effective vaccines. When antisera prepared against the main structural proteins of PERV were screened, a goat antiserum against the recombinant ectodomain of the transmembrane envelope protein p15E was found to neutralize PERV infectivity. Epitope mapping using overlapping peptides revealed two epitopes, E1 (GPQQLEK) and E2 (FEGWFN). These sequences are identical for all PERVs and are highly conserved among all gammaretroviruses. Interestingly, antibodies isolated from AIDS patients and specific for sequences of HIV-1 partially homologous with E2 (Mab4E10, LWNWFN) or located in close proximity to E2 (Ma62F5, ELDKWA) are known to neutralize several strains of HIV-1. It is the first report showing epitope mapping of gammaretrovirus-specific neutralizing antibodies and demonstrating similarity to corresponding epitopes in HIV. These domains of the transmembrane proteins of different retroviruses are an effective target for neutralizing antibodies and may be a useful antigen to create an antiretroviral vaccine. (C) 2003 Elsevier Science (USA). All rights reserved.