Chakrabarti S, Robert-Guroff M, Wong-Staal F, Gallo R C, Moss B
Nature. 1986;320(6062):535-7. doi: 10.1038/320535a0.
The discovery that the aetiological agent of acquired immune deficiency syndrome (AIDS) is a retrovirus, referred to as human T-lymphotropic virus type III (HTLV-III) or lymphadenopathy-associated virus (LAV) (for review see ref. 1), has raised the possibility of developing a vaccine. In this regard, the envelope (env) proteins of murine retroviruses can induce protective immunity in mice. The HTLV-III env gene specifies a primary polypeptide of approximately 860 amino acids that is glycosylated to form a precursor of relative molecular mass (Mr) 160,000 (gp160), which gives rise to mature membrane-associated proteins of Mr 120,000 (gp120) and 41,000 (gp41). The HTLV-III env gene has been expressed in Escherichia coli and by simian virus 40 (SV40) vectors but formation of the authentic proteins has not been demonstrated. Here, we describe the expression of the complete env gene by a vaccinia virus vector. Evidence is presented that synthesis, glycosylation, processing and membrane transport of the env polypeptide occurred without other HTLV-III gene functions; the env protein was recognized by sera from unrelated AIDs patients; and a single vaccination with the infectious recombinant vaccinia virus induced antibodies to gp120 in mice.
获得性免疫缺陷综合征(艾滋病)的病原体是一种逆转录病毒,称为人类T淋巴细胞嗜性病毒III型(HTLV-III)或淋巴结病相关病毒(LAV)(综述见参考文献1),这一发现增加了研发疫苗的可能性。在这方面,鼠逆转录病毒的包膜(env)蛋白可在小鼠中诱导保护性免疫。HTLV-III env基因编码一种约860个氨基酸的初级多肽,该多肽经糖基化形成相对分子质量(Mr)为160,000的前体(gp160),进而产生Mr为120,000(gp120)和41,000(gp41)的成熟膜相关蛋白。HTLV-III env基因已在大肠杆菌中以及通过猴病毒40(SV40)载体表达,但尚未证实有天然蛋白的形成。在此,我们描述了通过痘苗病毒载体表达完整的env基因。有证据表明,env多肽的合成、糖基化、加工和膜转运在没有其他HTLV-III基因功能的情况下发生;env蛋白可被无关艾滋病患者的血清识别;用感染性重组痘苗病毒单次接种可在小鼠中诱导产生针对gp120的抗体。