Hogervorst E, de Jong J, van Wijk A, Bakker M, Valk M, Nara P, Goudsmit J
Human Retrovirus Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands.
J Virol. 1995 Oct;69(10):6342-51. doi: 10.1128/JVI.69.10.6342-6351.1995.
The aim of the study was to investigate the influence of V3 loops from naturally occurring viruses on the neutralization sensitivity of a molecularly cloned virus. A selection of well-defined syncytium-inducing (SI) and non-SI V3 loops of a single human immunodeficiency virus type 1-infected individual (H594) and the V3 regions of two SI laboratory strains were inserted in an infectious molecular clone of human immunodeficiency type 1 LAI. Neutralization was performed with a heterologous serum pool and autologous patient serum, using the virus reduction neutralization assay and peripheral blood lymphocytes as target cells. High sensitivity of the chimeric viruses containing the laboratory strain V3 regions to neutralization by H594 sequential sera as well as the heterologous serum pool was found. A statistically significant correlation between the sensitivities of these viruses was seen. In contrast, insertion of the primary isolate NSI and SI envelope V3 loops significantly reduced the neutralization by autologous serum but not by the heterologous serum pool. No correlation was found between the neutralization of the viruses with laboratory strain-derived V3 regions and the viruses with primary isolate V3 domains. We conclude that heterologous antibodies are able to neutralize infectious molecular clones with V3 loops of both SI and NSI viruses, regardless of whether they originated from laboratory strains or primary isolates. However, serum of patient H594 discriminated between the two types of viruses and showed reduced neutralization of the viruses with the autologous NSI and SI primary isolate V3 loops. These results indicated that the neutralization sensitivity of the viruses depended on the capacity of the V3 region to influence the conformation of the virus envelope. These V3-dependent conformational changes partially explain the neutralization sensitivity of laboratory strains and the relative neutralization resistance of primary isolates.
本研究的目的是调查天然存在的病毒的V3环对分子克隆病毒中和敏感性的影响。从一名感染了单一1型人类免疫缺陷病毒（H594）的个体中挑选出明确的合胞体诱导（SI）和非SI V3环，以及两种SI实验室毒株的V3区域，将其插入到1型人类免疫缺陷病毒LAI的感染性分子克隆中。使用病毒减少中和试验，以异源血清池和患者自体血清进行中和试验，外周血淋巴细胞作为靶细胞。发现含有实验室毒株V3区域的嵌合病毒对H594序贯血清以及异源血清池的中和具有高敏感性。这些病毒的敏感性之间存在统计学上的显著相关性。相比之下，插入原代分离株的非SI和SI包膜V3环显著降低了自体血清的中和作用，但未降低异源血清池的中和作用。在具有实验室毒株来源的V3区域的病毒中和作用与具有原代分离株V3结构域的病毒中和作用之间未发现相关性。我们得出结论，异源抗体能够中和具有SI和非SI病毒V3环的感染性分子克隆，无论它们源自实验室毒株还是原代分离株。然而，患者H594的血清能够区分这两种类型的病毒，并且对具有自体非SI和SI原代分离株V3环的病毒的中和作用降低。这些结果表明，病毒的中和敏感性取决于V3区域影响病毒包膜构象的能力。这些V3依赖性构象变化部分解释了实验室毒株的中和敏感性和原代分离株的相对中和抗性。
