Joag S V, Li Z, Foresman L, Stephens E B, Zhao L J, Adany I, Pinson D M, McClure H M, Narayan O
Marion Merrell Dow Laboratory of Viral Pathogenesis and Department of Microbiology, University of Kansas Medical Center, Kansas City 66160-7420, USA.
J Virol. 1996 May;70(5):3189-97. doi: 10.1128/JVI.70.5.3189-3197.1996.
By animal-to-animal passage of simian/human immunodeficiency virus (SHIV) in pig-tailed macaques, we have developed a macaque model of human immunodeficiency virus type 1 (HIV-1) disease in humans. Passaging was begun with a chimeric virus containing the env gene of HIV-1 HXBc2 and the gag and pol genes of simian immunodeficiency virus SIVmac239. SHIV was passaged serially in cohorts of two macaques each, using bone marrow-to-bone marrow transfers at 5, 5, and 16 weeks for passages 2, 3, and 4, respectively. The fifth passage was done by using cell-free virus isolated from cerebrospinal fluid of a passage 4 macaque. The virus became more virulent with each passage. Virus replication was restricted in all three animals in passages 1 and 2 but not in five of the six animals in passages 3, 4, and 5. In these animals, intense virus replication in the lymphoid tissues resulted in almost total elimination of CD4+ T cells within weeks of inoculation, and three of these animals developed AIDS in less than 1 year. The more uniform virus-host interaction initiated by the cell-free virus in the passage 5 animals contrasted with a more variable pattern of disease initiated by infectious bone marrow cells during earlier passages. The virulent cell-free SHIV can now be used to screen the efficacy of vaccines directed against the envelope of HIV-1.
通过在猪尾猕猴中进行猿猴/人类免疫缺陷病毒（SHIV）的动物传代，我们建立了一种人类1型免疫缺陷病毒（HIV-1）疾病的猕猴模型。传代起始于一种嵌合病毒，其包含HIV-1 HXBc2的env基因以及猿猴免疫缺陷病毒SIVmac239的gag和pol基因。SHIV在每组两只猕猴中连续传代，分别在第5周、第5周和第16周通过骨髓到骨髓的移植进行第2、3和4代传代。第5代传代是通过使用从第4代猕猴脑脊液中分离出的无细胞病毒进行的。病毒在每次传代后毒性增强。在第1代和第2代时，病毒复制在所有三只动物中受到限制，但在第3、4和5代的六只动物中的五只中不受限。在这些动物中，淋巴组织中强烈的病毒复制导致接种后数周内CD4 + T细胞几乎完全清除，其中三只动物在不到1年的时间内发展为艾滋病。第5代动物中由无细胞病毒引发的病毒-宿主相互作用更为一致，这与早期传代过程中感染性骨髓细胞引发的疾病模式更具变异性形成对比。现在，毒性无细胞SHIV可用于筛选针对HIV-1包膜的疫苗的效力。
