COMPLEMENT CONTROL PROTEINS, CD46, CD55, AND CD59, AS COMMON SURFACE CONSTITUENTS OF HUMAN AND SIMIAN IMMUNODEFICIENCY VIRUSES AND POSSIBLE TARGETS FOR VACCINE PROTECTION
COMPLEMENT CONTROL PROTEINS, CD46, CD55, AND CD59, AS COMMON SURFACE CONSTITUENTS OF HUMAN AND SIMIAN IMMUNODEFICIENCY VIRUSES AND POSSIBLE TARGETS FOR VACCINE PROTECTION
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DOI：
10.1006/viro.1994.1622
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发表时间：
1994-11-15
期刊：
影响因子：
3.7
通讯作者：
JOHNSON, PR
中科院分区：
文献类型：
--
作者：
MONTEFIORI, DC;CORNELL, RJ;JOHNSON, PR
补体控制蛋白包括一组膜结合表面抗原，通过防止补体膜攻击复合物 (MAC) 的形成来保护细胞免遭补体裂解。已知 HIV-1 和 SIV 拥有细胞蛋白，因此其中一些蛋白可能有助于这些病毒逃避补体裂解的能力。通过流式细胞术发现三种补体控制蛋白CD46（膜辅因子蛋白）、CD55（衰变加速蛋白）和CD59（HRF20）在常用于HIV-1和SIV合成的CD4（+）细胞系的表面上表达。这些蛋白质的单克隆抗体沉淀了 CEMX174 细胞中合成的 HIV-1 IIIB 和 SIVdelta/B670 以及外周血单核细胞中合成的两种主要 HIV-1 分离株，表明在病毒从受感染细胞表面释放后，CD46、CD55 和 CD59 与病毒膜物理相关。额外的实验表明沉淀的材料含有感染性病毒，证实整个病毒被沉淀。当用人细胞生长的 SIV 免疫的猕猴血浆中的抗细胞抗体阻止抗 CD46 和抗 CD59 与 CEMX174 细胞表面结合时，发现了 CD46 和 CD59 在猕猴中具有免疫原性的证据。抗细胞抗体使 HIV-1 易于被补体裂解（通过 p24 核心蛋白的释放来测量），并且持续产生补体依赖性的 HIV-1 和 SIV 感染性降低 1-3 个对数。这些结果表明 CD46、CD55 和 CD59 是 HIV-1 和 SIV 的常见表面成分。这些结果还提出了一种可能性，即抗细胞抗体引起的 SIV 疫苗保护机制可能涉及补体介导的病毒溶解。 (C) 1994 年学术出版社
Complement control proteins include a group of membrane-bound surface antigens that protect cells from complement lysis by preventing formation of the membrane attack complex (MAC) of complement. HIV-1 and SIV are known to possess cellular proteins, making it possible that some of them contribute to the ability of these viruses to evade complement lysis. Three complement control proteins, CD46 (membrane cofactor protein), CD55 (decay accelerating protein), and CD59 (HRF20), were found by flow cytometry to be expressed on the surface of CD4(+) cell lines commonly used for HIV-1 and SIV synthesis. Monoclonal antibodies to each of these proteins precipitated HIV-1 IIIB and SIVdelta/B670 synthesized in CEMX174 cells and two primary HIV-1 isolates synthesized in peripheral blood mononuclear cells, indicating that CD46, CD55, and CD59 are physically associated with the virus membrane after the virus has been released from the surface of infected cells. Additional experiments showed that the precipitated material contained infectious virus, confirming that whole virus was precipitated. Evidence that CD46 and CD59 are immunogenic in macaques was found when anti-cell antibodies in plasmas from macaques immunized with human cell-grown SIV blocked anti-CD46 and anti-CD59 from binding to the surface of CEMX174 cells. Anti-cell antibodies rendered HIV-1 susceptible to complement lysis as measured by the release of p24 core protein, and consistently produced a complement-dependent reduction in HIV-1 and SIV infectivity of 1-3 logs. These results demonstrate that CD46, CD55, and CD59 are common surface constituents of HIV-1 and SIV. The results also raise the possibility that the mechanism of SIV vaccine protection attributed to anti-cell antibodies could have involved complement-mediated virolysis. (C) 1994 Academic Press, Inc.