Processing, assembly, and immunogenicity of human immunodeficiency virus core antigens expressed by recombinant vaccinia virus.
Processing, assembly, and immunogenicity of human immunodeficiency virus core antigens expressed by recombinant vaccinia virus.
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重组牛痘病毒表达的人类免疫缺陷病毒核心抗原的加工、组装和免疫原性。
DOI：
10.1016/0042-6822(90)90300-g
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发表时间：
1990
期刊：
影响因子：
3.7
通讯作者：
Alpers,C
中科院分区：
文献类型：
--
作者：
Hu,SL;Travis,BM;Garrigues,J;Zarling,JM;Sridhar,P;Dykers,T;Eichberg,JW;Alpers,C
构建了含有人类免疫缺陷病毒1型（HIV-1） gag-polopen阅读框区域的重组痘苗病毒。被同时含有抗原和蛋白酶基因的重组体感染的细胞能有效地表达和加工hiv抗原。在被只含有gag而不含蛋白酶基因的重组病毒感染的细胞中，加工过程大大减少。然而，蛋白酶缺陷重组产生了大量的p41。该蛋白与p24特异性单克隆抗体具有免疫反应性，并通过在gagorf的p5编码区含有3 '缺失的重组蛋白以截断形式产生。这些结果表明p41可能是一种替代前体，其n端序列来自p24， c端序列来自p5。重组感染细胞的超微结构分析表明，表达的gag抗原被组装成逆转录病毒样颗粒并分泌到培养基中。这种组装过程不依赖于HIV蛋白酶的功能，因为不成熟的核心颗粒是由缺乏HIV-1蛋白酶功能的重组体产生的。用牛痘- hiv组合病毒免疫小鼠和黑猩猩可产生针对hiv抗原的抗体和细胞介导的免疫应答。因此，这些重组体不仅可用于研究HIV病毒粒子的加工和组装，而且可用于设计用于艾滋病预防和免疫治疗的免疫原。
Recombinant vaccinia viruses that contained regions of thegag-polopen reading frames of human immunodeficiency virus type 1 (HIV-1) were constructed. Cells infected with recombinants containing bothgagand protease genes expressed and processed HIVgagantigens efficiently. Processing was much reduced in cells infected with recombinants containing onlygag, but not the protease gene. However, significant amounts of p41 were produced by proteaseddefective recombinants. This protein was immunoreactive with p24-specific monoclonal antibodies and was produced in a truncated form by a recombinant containing a 3′ deletion in the pt 5 coding region ofgagORF. These results indicate that p41 could represent an alternativegagprecursor with N-terminal sequences derived from p24 and C-terminal from pt 5. Ultrastructural analysis of recombinant-infected cells revealed that thegagantigens expressed were assembled into retrovirus-like particles and were secreted into culture medium. This assembly process was not dependent on HIV protease function, because immature core particles were produced by recombinants lacking HIV-1 protease functions. Immunization of mice and chimpanzees with vaccinia-HIVgagrecombinant viruses generated both antibody and cell-mediated immune responses to HIVgagantigens. These recombinants are therefore useful not only for studying HIV virion processing and assembly, but also for designing immunogens for the prophylaxis and immuno-therapy against AIDS.