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1型人类免疫缺陷病毒（HIV-1）蛋白酶变体的细胞内表达可抑制野生型和蛋白酶抑制剂耐药型HIV-1毒株在人T细胞系中的复制。

Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines.

作者信息

Junker U, Escaich S, Plavec I, Baker J, McPhee F, Rose J R, Craik C S, Böhnlein E

机构信息

Progenesys Program at Systemix, Palo Alto, California 94304, USA.

出版信息

J Virol. 1996 Nov;70(11):7765-72. doi: 10.1128/JVI.70.11.7765-7772.1996.

DOI:10.1128/JVI.70.11.7765-7772.1996
PMID:8892897
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC190846/
Abstract

The enzymatic activity of the human immunodeficiency type 1 (HIV-1) protease (PR) is crucial to render HIV-1 virions mature and infectious. Hence, genetic intervention strategies based on trans-dominant (td) variants of the HIV-1 PR might be an alternative to current pharmacological and gene therapy regimens for AIDS. CD4-positive human CEM-SS T-cell lines were generated which constitutively expressed HIV-1 td PR variants. HIV-1 infection experiments demonstrated severely reduced HIV-1 replication in these td PR CEM-SS cell lines compared with control T cells expressing wild-type PR. Furthermore, replication of an HIV-1 isolate bearing a PR inhibitor-resistant PR was blocked, showing that genetic intervention strategies based on td PRs can be effective against HIV-1 isolates containing PR inhibitor-resistant mutants.

摘要

人类免疫缺陷病毒1型（HIV-1）蛋白酶（PR）的酶活性对于使HIV-1病毒体成熟并具有传染性至关重要。因此，基于HIV-1 PR的反式显性（td）变体的基因干预策略可能是目前用于治疗艾滋病的药理学和基因治疗方案的替代方法。构建了持续表达HIV-1 td PR变体的CD4阳性人类CEM-SS T细胞系。HIV-1感染实验表明，与表达野生型PR的对照T细胞相比，这些td PR CEM-SS细胞系中的HIV-1复制严重减少。此外，携带对PR抑制剂耐药的PR的HIV-1分离株的复制被阻断，这表明基于td PRs的基因干预策略可有效对抗含有PR抑制剂耐药突变体的HIV-1分离株。

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Intracellular expression of human immunodeficiency virus type 1 (HIV-1) protease variants inhibits replication of wild-type and protease inhibitor-resistant HIV-1 strains in human T-cell lines.1型人类免疫缺陷病毒（HIV-1）蛋白酶变体的细胞内表达可抑制野生型和蛋白酶抑制剂耐药型HIV-1毒株在人T细胞系中的复制。
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Trans-dominant inhibitory human immunodeficiency virus type 1 protease monomers prevent protease activation and virion maturation.反式显性抑制性人类免疫缺陷病毒1型蛋白酶单体可阻止蛋白酶激活和病毒体成熟。
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