Chimeric simian human immunodeficiency virus that causes progressive loss of CD4(+) T cells and AIDS in pig-tailed macaques
Chimeric simian human immunodeficiency virus that causes progressive loss of CD4(+) T cells and AIDS in pig-tailed macaques
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DOI：
10.1128/jvi.70.5.3189-3197.1996
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发表时间：
1996-05-01
影响因子：
5.4
通讯作者：
Narayan, O
中科院分区：
文献类型：
--
作者：
Joag, SV;Li, Z;Narayan, O
通过猴/人免疫缺陷病毒（SHIV）在猪尾猕猴中的动物间传代，我们建立了人免疫缺陷病毒1型（HIV-1）疾病的猕猴模型。传代开始于含有HIV-1 HXBc 2的env基因和猴免疫缺陷病毒SIVmac 239的gag和pol基因的嵌合病毒。SHIV在每组两只猕猴的队列中连续传代，分别在第2、3和4代的第5、5和16周使用骨髓-骨髓转移。通过使用从第4代猕猴的脑脊液中分离的无细胞病毒进行第5代。病毒的毒性随着每次传代而变得更强，病毒复制在第1代和第2代的所有三只动物中受到限制，但在第3代、第4代和第5代的六只动物中的五只动物中没有受到限制，在这些动物中，淋巴组织中强烈的病毒复制导致在接种后几周内CD 4（+）T细胞几乎完全消除，其中三只动物在不到1年的时间内患上了艾滋病，在第5代动物中，无细胞病毒引发的病毒与宿主相互作用更加均匀，而在早期传代期间，感染性骨髓细胞引发的疾病模式更加多变。现在可以使用强毒无细胞SHIV来筛选针对HIV-1包膜的疫苗的功效。
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.