Jurkiewicz E, Hunsmann G, Schäffner J, Nisslein T, Lüke W, Petry H
Department of Virology and Immunology, German Primate Centre, Göttingen.
J Virol. 1997 Dec;71(12):9475-81. doi: 10.1128/JVI.71.12.9475-9481.1997.
The sequence variability of viral structure polypeptides has been associated with immune escape mechanisms. The V1 region of simian immunodeficiency virus (SIV) is a highly variable region of the SIVmac env gene. Here, we describe the V1 region as a linear neutralizing epitope. V1 region-specific neutralizing antibodies (NAb) were first demonstrated in a rabbit infected with a recombinant vaccinia virus carrying the env gene of human immunodeficiency virus type 2 strain ben (HIV-2ben). Since we detected in this animal V1 region-specific NAb that were able to neutralize not only human immunodeficiency virus type 2 but also SIVmac32H, we investigated whether a similar immune response is evoked in macaques (Macaca mulatta) either infected with SIVmac or immunized with the external glycoprotein (gp130) of the same virus. Distinctly lower NAb titers were found in the SIVmac-infected animals than in the gp130-immunized macaques. Since the NAb titers in both groups were high enough for competition experiments, we used five overlapping peptides encompassing the whole V1 region for a detailed identification of the epitope. In each of the 12 macaques investigated, we detected a high level of NAb reacting with at least one peptide located in the central part of the V1 region. The relatively high degree of divergence, especially within the central part of the V1 region, which characterized the evolution of the retroviral sequences from the original inoculum in the infected macaques suggests the development of escape mutants. Furthermore, 3 of 12 animals developed NAb directed against the amino-terminal end of the V1 region epitope. Sequence analysis, however, revealed relatively low levels of genetic drift and genetic variability within this part of the V1 region. The induction of V1 env-specific NAb not only in gp130-immunized macaques but also in SIVmac-infected animals in combination with the increased genetic variability of this region in vivo indicates a marked biological significance of this epitope for the virus.
病毒结构多肽的序列变异性与免疫逃逸机制相关。猴免疫缺陷病毒（SIV）的V1区是SIVmac env基因的一个高度可变区。在此，我们将V1区描述为一个线性中和表位。V1区特异性中和抗体（NAb）首先在感染携带2型人类免疫缺陷病毒ben株（HIV - 2ben）env基因的重组痘苗病毒的兔子中得到证实。由于我们在该动物中检测到了能够中和不仅2型人类免疫缺陷病毒而且还有SIVmac32H的V1区特异性NAb，我们研究了在感染SIVmac或用同一病毒的外膜糖蛋白（gp130）免疫的猕猴（恒河猴）中是否引发了类似的免疫反应。在感染SIVmac的动物中发现的NAb滴度明显低于用gp130免疫的猕猴。由于两组中的NAb滴度都高到足以进行竞争实验，我们使用了涵盖整个V1区的五个重叠肽来详细鉴定表位。在研究的12只猕猴中的每一只中，我们都检测到高水平的NAb与位于V1区中部的至少一个肽发生反应。相对较高的分歧程度，特别是在V1区中部，这是感染猕猴中逆转录病毒序列从原始接种物进化的特征，提示了逃逸突变体的产生。此外，12只动物中有3只产生了针对V1区表位氨基末端的NAb。然而，序列分析显示该V1区这一部分内的遗传漂变和遗传变异性相对较低。V1 env特异性NAb不仅在gp130免疫的猕猴中诱导产生，而且在SIVmac感染的动物中也诱导产生，再加上该区域在体内增加的遗传变异性，表明该表位对病毒具有显著的生物学意义。
