更新于：2024-11-01

HIV envelope protein gp120 x CD4 x CCR5

更新于：2024-11-01

基本信息

关联

项与 HIV envelope protein gp120 x CD4 x CCR5 相关的药物

AAV-eCD4-Ig

靶点

CCR5 x CD4 x HIV envelope protein gp120

作用机制

CCR5拮抗剂 [+2]

在研机构

The Scripps Research Institute

原研机构

The Scripps Research Institute

在研适应症

HIV感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 HIV envelope protein gp120 x CD4 x CCR5 相关的临床结果

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100 项与 HIV envelope protein gp120 x CD4 x CCR5 相关的转化医学

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0 项与 HIV envelope protein gp120 x CD4 x CCR5 相关的专利（医药）

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项与 HIV envelope protein gp120 x CD4 x CCR5 相关的文献（医药）

2015-06-03·Expert Opinion on Therapeutic Targets2区 · 医学

HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth

2区 · 医学

Review

作者: Carole A Bewley ; Sabrina Lusvarghi ; Priyamvada Acharya ; Peter D Kwong

INTRODUCTIONThe HIV-1 gp120 envelope (Env) glycoprotein mediates attachment of virus to human target cells that display requisite receptors, CD4 and co-receptor, generally CCR5. Despite high-affinity interactions with host receptors and proof-of-principle by the drug maraviroc that interference with CCR5 provides therapeutic benefit, no licensed drug currently targets gp120.AREAS COVEREDAn overview of the role of gp120 in HIV-1 entry and of sites of potential gp120 vulnerability to therapeutic inhibition is presented. Viral defenses that protect these sites and turn gp120 into a moving labyrinth are discussed together with strategies for circumventing these defenses to allow therapeutic targeting of gp120 sites of vulnerability.EXPERT OPINIONThe gp120 envelope glycoprotein interacts with host proteins through multiple interfaces and has conserved structural features at these interaction sites. In spite of this, targeting gp120 for therapeutic purposes is challenging. Env mechanisms that have evolved to evade the humoral immune response also shield it from potential therapeutics. Nevertheless, substantial progress has been made in understanding HIV-1 gp120 structure and its interactions with host receptors, and in developing therapeutic leads that potently neutralize diverse HIV-1 strains. Synergies between advances in understanding, needs for therapeutics against novel viral targets and characteristics of breadth and potency for a number of gp120-targetting lead molecules bodes well for gp120 as a HIV-1 therapeutic target.

2012-06-01·Journal of Neuroimmune Pharmacology3区 · 医学

Genetic Knockouts Suggest a Critical Role for HIV Co-Receptors in Models of HIV gp120-Induced Brain Injury

3区 · 医学

Review

作者: Natalia E. Sejbuk ; Ricky Maung ; Maya K. Desai ; Rossella Russo ; Marcus Kaul ; Kathryn E. Medders

Infection with HIV-1 frequently affects the brain and causes NeuroAIDS prior to the development of overt AIDS. The HIV-1 envelope protein gp120 interacts with host CD4 and chemokine co-receptors to initiate infection of macrophages and lymphocytes. In addition, the virus or fragments of it, such as gp120, cause macrophages to produce neurotoxins and trigger neuronal injury and apoptosis. Moreover, the two major HIV co-receptors, the chemokine receptors CCR5 and CXCR4, serve numerous physiological functions and are widely expressed beyond immune cells, including cells in the brain. Therefore, HIV co-receptors are poised to play a direct and indirect part in the development of NeuroAIDS. Although rodents are not permissive to infection with wild type HIV-1, viral co-receptors - more than CD4 - are highly conserved between species, suggesting the animals can be suitable models for mechanistic studies addressing effects of receptor-ligand interaction other than infection. Of note, transgenic mice expressing HIV gp120 in the brain share several pathological hallmarks with NeuroAIDS brains. Against this background, we will discuss recently completed or initiated, ongoing studies that utilize HIV co-receptor knockout and viral gp120-transgenic mice as models for in vitro and in vivo experimentation in order to address the potential roles of HIV gp120 and its co-receptors in the development of NeuroAIDS.

2004-07-16·Journal of Leukocyte Biology3区 · 医学

R5 HIV gp120-mediated cellular contacts induce the death of single CCR5-expressing CD4 T cells by a gp41-dependent mechanism

3区 · 医学

Article

作者: Esté, José A ; Blanco, Julià ; Clotet, Bonaventura ; Barretina, Jordi

AbstractThe use of CXC chemokine receptor 4 (CXCR4) and CC chemokine receptor 5 (CCR5) by X4 and R5 human immunodeficiency virus (HIV) envelopes (Env) influences HIV cytopathicity. Here, we have evaluated the role of CCR5 and gp41 in Env-induced cell death occurring during the contacts of uninfected, primary cells with MOLT cells infected with different R5 and X4 HIV isolates. As reported for X4-Env, R5 HIV-infected cells destroyed CD4 T cells expressing the appropriate coreceptor by inducing the formation of syncytia and the death of single target cells. Therefore, only the small (<10%) CCR5+ subset of primary CD4 T cells was sensitive to cellular presentation of R5-Env, and CCR5–CD4 T cells showed complete resistance to R5-Env-mediated cell death. X4- and R5-infected cells killed single primary cells by a common mechanism that was dependent on gp41 function and induced a rapid loss of mitochondrial membrane potential and plasma membrane integrity in target cells. Single-cell death was not affected by the blockade of HIV replication in target cells or G-protein signaling through CXCR4/CCR5. In contrast, caspase inhibition (Z-Val-Ala-Asp-fluoromethylketone) profoundly changed the outcome of cell-to-cell contacts by reducing the number of single dead CD4 T cells and increasing the rate of syncytium formation. In conclusion, X4 and R5 HIV Env share a common gp41-dependent mechanism to kill CD4 T cells during cellular contacts. Env tropism and coreceptor expression but not differential killing mechanisms seem to govern the extent of cytopathic effects induced by HIV infection.