Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells
Generation of HIV-1 derivatives that productively infect macaque monkey lymphoid cells
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DOI：
10.1073/pnas.0608289103
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发表时间：
2006-11-07
影响因子：
11.1
通讯作者：
Adachi, Akio
中科院分区：
文献类型：
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作者：
Kamada, Kazuya;Igarashi, Tatsuhiko;Adachi, Akio
人类免疫缺陷病毒1型（HIV-1）的宿主范围狭窄，部分是由先天细胞因子引起的，例如载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC 3G）和TRIM 5 alpha，它们限制病毒在猴细胞中的复制。构建了含有21个核苷酸的猿猴免疫缺陷病毒（SIV）Gag CA元件（对应于HIV-1亲环素A结合位点）和整个SIV vif基因的变体HIV-1分子克隆。在食蟹猴淋巴样细胞系中的长期传代导致获得env中的两个非同义变化，这赋予了改善的复制特性。一个前病毒分子克隆，来自感染的细胞和指定的NL-DT 5 R，用于产生病毒股票能够建立传播感染的食蟹猴T细胞系和CD 8-耗尽的外周血单核细胞从五个猪尾猕猴和三个恒河猴之一。NL-DT 5 R，其在遗传上是> 93%的HIV-1，提供了在广泛的非人灵长类物种中分析多个HIV-1基因的功能的机会，这是目前可用的SIV/HIV嵌合病毒不可能的。
The narrow host range of human immunodeficiency virus type 1 (HIV-1) is caused in part by innate cellular factors such as apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) and TRIM5 alpha, which restrict virus replication in monkey cells. Variant HIV-1 molecular clones containing both a 21-nucleotide simian immunodeficiency virus (SIV) Gag CA element, corresponding to the HIV-1 cyclophilin A-binding site, and the entire SIV vif gene were constructed. Long-term passage in a cynomolgus monkey lymphoid cell line resulted in the acquisition of two nonsynonymous changes in env, which conferred improved replication properties. A proviral molecular clone, derived from infected cells and designated NL-DT5R, was used to generate virus stocks capable of establishing spreading infections in the cynomolgus monkey T cell line and CD8-depleted peripheral blood mononuclear cells from five of five pig-tailed macaques and one of three rhesus monkeys. NL-DT5R, which genetically is > 93% HIV-1, provides the opportunity, not possible with currently available SIV/HIV chimeric viruses, to analyze the function of multiple HIV-1 genes in a broad range of nonhuman primate species.