4.6 Article

Soluble CD4 and low molecular weight CD4-mimetic compounds sensitize cells to be killed by anti-HIV cytotoxic immunoconjugates

期刊

JOURNAL OF VIROLOGY
卷 -, 期 -, 页码 -

出版社

AMER SOC MICROBIOLOGY
DOI: 10.1128/jvi.01154-23

关键词

HIV cure; cytotoxic immunoconjugate; soluble CD4; CD4 mimetic; HIV envelope; gp41 and gp120; immunotoxin; human immunodeficiency virus

类别

向作者/读者索取更多资源

The reservoir of HIV-infected cells that persist despite anti-retroviral therapy is the main barrier to curing HIV infection. One proposed approach to eliminate these cells is using cytotoxic immunoconjugates targeting the HIV envelope protein. This study explores the effects of different forms of CD4 and a CD4-mimetic molecule on cells expressing the virus's envelope protein.
The reservoir of HIV-infected cells that persist in the face of effective anti-retroviral therapy (ART) is the barrier to curing HIV infection. These long-lived CD4+ cells carry a functional provirus that can become activated upon immune stimulation. When ART is stopped, this leads to a rapid rebound in viremia. A variety of approaches are proposed to eliminate these cells, many dependent upon the expression of virus proteins. We are examining the use of cytotoxic immunoconjugates targeting the HIV envelope protein (Env) as a method to eradicate cells producing virus and have demonstrated that soluble CD4 enhances the cytotoxic effect of gp41-targeted immunoconjugates. Mechanisms include increased antigen exposure and greater internalization of the immunoconjugate. Here we have tested different protein forms of CD4 and the small molecule CD4-mimetic BNM-III-170 for their effects on cells expressing cell-surface Env. Effects studied include sensitization to immunoconjugate killing, cell surface antigen expression, viability, and virus secretion. The CD4 proteins and BNM-III-170 produced comparable effects in these Env-expressing cell lines, each sensitizing cells to cytotoxicity by anti-gp41 immunoconjugates. The results provide further evidence that low molecular weight CD4 mimetics produce biologic effects similar to those caused by soluble CD4 itself and suggest additional therapeutic uses for these molecules.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据