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在病毒长末端重复序列控制下表达的细胞内CD4对CD4+ T细胞中1型人类免疫缺陷病毒产生的阻断作用。

Blockade of human immunodeficiency virus type 1 production in CD4+ T cells by an intracellular CD4 expressed under control of the viral long terminal repeat.

作者信息

Buonocore L, Rose J K

机构信息

Department of Pathology, Yale University School of Medicine, New Haven, CT 06510.

出版信息

Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2695-9. doi: 10.1073/pnas.90.7.2695.

Abstract

A retroviral vector was constructed in which a gene encoding a mutated soluble CD4 protein that is retained in the endoplasmic reticulum (sCD4-KDEL) is expressed under control of human immunodeficiency virus type 1 (HIV-1) regulatory elements. HIV-1 infection of a human T-cell line transduced with this vector led to induction of sCD4-KDEL synthesis and a block in transport of the HIV envelope protein to the cell surface. There was a complete block to maturation of infectious HIV-1 in the transduced cells, no viral spread, and little or no syncytium formation. Infected cells gradually disappeared from the culture over a period of 2 months. This intracellular trap for HIV has potential application in gene therapy for AIDS.

摘要

构建了一种逆转录病毒载体,其中编码在内质网中滞留的突变型可溶性CD4蛋白(sCD4-KDEL)的基因在人类免疫缺陷病毒1型(HIV-1)调控元件的控制下表达。用该载体转导的人类T细胞系感染HIV-1导致sCD4-KDEL合成的诱导以及HIV包膜蛋白向细胞表面运输的阻断。在转导的细胞中,感染性HIV-1的成熟完全受阻,没有病毒传播,并且几乎没有或没有合胞体形成。在2个月的时间内,感染的细胞逐渐从培养物中消失。这种针对HIV的细胞内陷阱在艾滋病的基因治疗中具有潜在的应用价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ac7/46162/cbd3ea8eefba/pnas01466-0149-a.jpg

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