Klinger J M, Himathongkham S, Legg H, Luciw P A, Barnett S W
Chiron Corporation, Emeryville 94608, USA.
AIDS. 1998 May 28;12(8):849-57. doi: 10.1097/00002030-199808000-00006.
To construct an infectious chimeric simian immunodeficiency virus/HIV-1 (SHIV) with the envelope of a Thai subtype E HIV-1 strain for use in a non-human primate model.
A novel SHIV genome was derived using the sequences of the ectodomain of the envelope gene from the Thai subtype E strain, HIV-1(9466). This SHIV (SHIV9466.33) was recovered by cocultivation from human peripheral blood mononuclear cells (PBMC) after transfection of human rhabdosarcoma cells. Rhesus macaque and baboon PBMC were screened in vitro for susceptibility to infection with SHIV9466.33. After successful infection of baboon PBMC, four animals were inoculated intravenously with SHIV9466.33 and monitored for plasma viral RNA, virus isolation from the PBMC, seroconversion, T-cell subsets, and signs of disease.
SHIV9466.33 was able to infect PBMC from 12 out of 14 baboons. All four of the baboons selected for in vivo inoculation became infected. Peak plasma viral RNA levels of 8000 to 700,000 RNA copies/ml were measured at 2 weeks post-inoculation. Virus was isolated from the PBMC of all four baboons during acute infection, and all seroconverted. Although transient declines in CD4+ T-cells were observed during early infection, CD4+ levels remained within normal ranges thereafter. In contrast, in vitro cultures of PBMC of four rhesus macaques were not susceptible to infection with SHIV9466.33.
SHIV9466.33 containing an HIV-1 subtype E envelope displayed tropism for baboon PBMC but not for rhesus macaque PBMC. This chimeric virus established infection and induced antiviral antibodies in baboons inoculated by the intravenous route with cell-free virus. Thus, infection of baboons with SHIV9466.33 will serve as an important animal model for future studies of HIV-1 vaccine efficacy.
构建一种具有泰国E亚型HIV-1毒株包膜的感染性嵌合猴免疫缺陷病毒/ HIV-1（SHIV），用于非人灵长类动物模型。
利用泰国E亚型毒株HIV-1(9466)包膜基因胞外域序列构建新型SHIV基因组。将人横纹肌肉瘤细胞转染后，通过与人外周血单核细胞（PBMC）共培养获得该SHIV（SHIV9466.33）。对恒河猴和狒狒的PBMC进行体外筛选，检测其对SHIV9466.33感染的易感性。成功感染狒狒PBMC后，对4只动物静脉接种SHIV9466.33，并监测血浆病毒RNA、PBMC中的病毒分离情况、血清转化、T细胞亚群及疾病体征。
SHIV9466.33能够感染14只狒狒中12只的PBMC。选作体内接种的4只狒狒均被感染。接种后2周测得血浆病毒RNA峰值水平为8000至700,000 RNA拷贝/毫升。在急性感染期间，从所有4只狒狒的PBMC中均分离出病毒，且均发生血清转化。虽然在早期感染期间观察到CD4 + T细胞短暂下降，但此后CD4 +水平仍保持在正常范围内。相比之下，4只恒河猴的PBMC体外培养物对SHIV9466.33感染不敏感。
含有HIV-1 E亚型包膜的SHIV9466.33对狒狒PBMC具有嗜性，但对恒河猴PBMC无嗜性。这种嵌合病毒通过静脉途径接种无细胞病毒后在狒狒体内建立感染并诱导抗病毒抗体。因此，用SHIV9466.33感染狒狒将成为未来HIV-1疫苗效力研究的重要动物模型。
