Mamounas M, Looney D J, Talbott R, Wong-Staal F
Department of Medicine, University of California, San Diego, La Jolla 92093-0665, USA.
J Virol. 1995 Oct;69(10):6424-9. doi: 10.1128/JVI.69.10.6424-6429.1995.
The human immunodeficiency virus type 1 strain MN (HIV-1MN) principal neutralizing determinant (PND, V3 loop) was introduced into infectious molecular clones HIV-2KR and simian immunodeficiency virus mm239 (SIVmm239) by hybridization PCR, replacing the corresponding HIV-2 or SIV envelope cysteine loops with the HIV-1 coding sequence. The HIV-2 chimera (HIV-2KR-MNV3) was found to be capable of infecting a number of T-cell lymphoblastic cell lines as well as primary peripheral blood mononuclear cells. In contrast, the SIV chimera (SIV239MNV3) was not replication competent. Envelope produced by HIV-2KR-MNV3 but not the parental HIV-2KR was recognized by V3-specific and HIV-1-specific polyclonal antisera in radioimmunoprecipitation assays. HIV-2-specific antisera recognized both the chimeric and parental virus but not HIV-1MN. The chimeric HIV-2KR-MNV3 virus proved to be exquisitely susceptible to neutralization by HIV-1-specific and V3-specific antisera, suggesting the potential for use in animal models designed to test HIV-1 vaccine candidates which target the PND.
通过杂交聚合酶链反应(PCR),将1型人类免疫缺陷病毒MN株(HIV-1MN)主要中和决定簇(PND,V3环)导入感染性分子克隆HIV-2KR和猴免疫缺陷病毒mm239(SIVmm239),用HIV-1编码序列取代相应的HIV-2或SIV包膜半胱氨酸环。发现HIV-2嵌合体(HIV-2KR-MNV3)能够感染多种T细胞淋巴母细胞系以及原代外周血单核细胞。相比之下,SIV嵌合体(SIV239MNV3)没有复制能力。在放射免疫沉淀试验中,HIV-2KR-MNV3产生的包膜而非亲本HIV-2KR产生的包膜能被V3特异性和HIV-1特异性多克隆抗血清识别。HIV-2特异性抗血清能识别嵌合病毒和亲本病毒,但不能识别HIV-1MN。嵌合HIV-2KR-MNV3病毒被证明对HIV-1特异性和V3特异性抗血清的中和作用极为敏感,这表明其有潜力用于旨在测试针对PND的HIV-1候选疫苗的动物模型。