CONSTRUCTION AND IN-VITRO PROPERTIES OF HIV-1 MUTANTS WITH DELETIONS IN NONESSENTIAL GENES
CONSTRUCTION AND IN-VITRO PROPERTIES OF HIV-1 MUTANTS WITH DELETIONS IN NONESSENTIAL GENES
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DOI：
10.1089/aid.1994.10.343
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发表时间：
1994-04-01
影响因子：
1.5
通讯作者：
DESROSIERS, RC
中科院分区：
文献类型：
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作者：
GIBBS, JS;REGIER, DA;DESROSIERS, RC
在所有已知的慢病毒中发现了对细胞培养中的病毒复制不是必需的辅助基因。HIV-1的“非必需”辅助基因是vif、vpr、vpu和nef。LTR中U3上游区域内的序列也不是细胞培养物中病毒复制所需的。我们在野生型HIV-1感染性分子克隆NL 4 -3中构建了一组23个在这些区域中具有单一和组合缺失的突变体。vpu、vpr和nef基因以及U3上游序列（US）的缺失（单独或组合）不会明显改变黑猩猩PBMC、人PBMC或B/T细胞杂交系CEMx 174中的病毒复制。相比之下，vif基因的缺失显著延迟了病毒在所有三种细胞类型中的复制。这些HIV-1缺失突变体的收集将有助于阐明这些基因的功能和研究动物模型中的抗病毒免疫。
Auxiliary genes that are not essential for viral replication in cell culture are found in all known lentiviruses. The ''nonessential'' auxiliary genes of HIV-1 are vif, vpr, vpu, and nef. Sequences within the upstream region of U3 in the LTR are also not required for virus replication in cell culture. We constructed a panel of 23 mutants with single and combination deletions in these regions in the wild-type HIV-1 infectious molecular clone NL4-3. Deletion of the vpu, vpr, and nef genes and the U3 upstream sequence (US), individually or in combinations, did not appreciably alter virus replication in either chimpanzee PBMCs, human PBMCs, or in the B/T cell hybrid line CEMx174. In contrast, deletion of the vif gene dramatically delayed virus replication in all three cell types. This collection of HIV-1 deletion mutants will be useful for elucidating the functions of these genes and for investigating antiviral immunity in animal models.