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APOBEC3G mediated resistance to HIV-1 infection

Reactome ID: R-HSA-180689

中文名称

APOBEC3G介导的HIV-1感染抵抗

通路描述

APOBEC3家族成员提供对外源性和内源性逆转录病毒的先天抵抗(见Cullen 2006年近期综述)。人类和其他灵长类动物编码七个不同的胞嘧啶脱氨酶簇,其中APOBEC3G、APOBEC3F和APOBEC3B具有部分抗HIV-1活性。我们对APOBEC3G的理解最为完整,该酶首先被描述,本文所述反应将针对该代表性酶。APOBEC3G是一种胞质蛋白,强烈限制Vif缺陷HIV-1的复制。它表达于易受HIV感染的细胞群中(例如T淋巴细胞和巨噬细胞)。在产生细胞中,APOBEC3G通过与HIV-1 Gag核糖核蛋白(NC)蛋白的相互作用,以RNA依赖性方式被整合到出芽的HIV-1颗粒中。在新生感染细胞(=靶细胞)中,病毒相关的APOBEC3G通过逆转录过程中在负链病毒DNA中间体中将胞嘧啶脱氨化为尿嘧啶来调节HIV-1的感染性。脱氨化导致正链病毒DNA中诱导G到A超突变,这些突变随后可以整合为非功能性前病毒或降解,在整合之前。
英文描述
APOBEC3G mediated resistance to HIV-1 infection Representatives of the apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) family provide innate resistance to exogeneous and endogenous retroviruses (see Cullen 2006 for a recent review). Humans and other primates encode a cluster of seven different cytidine deaminases with APOBEC3G, APOBEC3F and APOBEC3B having some anti HIV-1 activity. Our understanding is most complete for APOBEC3G which has been described first and the reactions described herein will focus on this representative enzyme.

APOBEC3G is a cytoplasmic protein which strongly restricts replication of Vif deficient HIV-1 (Sheehy 2002). It is expressed in cell populations that are susceptible to HIV infection (e.g., T-lymphocytes and macrophages). In the producer cell, APOBEC3G is incorporated into budding HIV-1 particles through an interaction with HIV-1 gag nucleocapsid (NC) protein in a RNA-dependent fashion.

Within the newly infected cell (= target cell), virus-associated APOBEC3G regulates the infectivity of HIV-1 by deaminating cytidine to uracil in the minus-strand viral DNA intermediate during reverse transcription. Deamination results in the induction of G-to-A hypermutations in the plus-strand viral DNA which subsequently can either be integrated as a non-functional provirus or degraded before integration.

所含基因

6 个基因