APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-1.
APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-1.
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APOBEC3 降解是 HIV-1 Vif 在骨髓细胞系 THP-1 中进行病毒复制的主要功能。
DOI：
10.1101/2023.03.28.534666
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Harris,ReubenS
中科院分区：
文献类型：
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作者：
Ikeda,Terumasa;Shimizu,Ryo;Nasser,Hesham;Carpenter,MichaelA;Cheng,AdamZ;Brown,WilliamL;Sauter,Daniel;Harris,ReubenS
HIV-1必须克服多种先天性抗病毒机制才能在CD 4 + T淋巴细胞和巨噬细胞中复制。先前的研究已经证明，APOBEC 3（A3）蛋白家族（至少A3 D、A3 F、A3 G和稳定的A3 H单倍型）有助于HIV-1在CD 4 + T淋巴细胞中的限制。病毒编码的病毒粒子感染因子（Vif）通过降解A3酶来抵消这种抗病毒活性，从而使HIV-1在感染细胞中复制。除了A3蛋白，Vif还靶向CD 4 + T淋巴细胞中的其他细胞蛋白，包括PPP 2 R5蛋白。然而，Vif是否主要只降解A3蛋白或在病毒复制过程中具有额外的必需靶点目前尚不清楚。在此，我们描述了A3 F-、A3 F/A3 G-和A3 A-至-A3 G-无效THP-1细胞的开发和表征。与Vif-proficient HIV-1相比，Vif-deficient病毒在亲本和A3 F-无效THP-1细胞中的感染性显著降低，并且在A3 F/A3 G-无效细胞中的感染性降低更适度。值得注意的是，A3 A-A3 G蛋白表达的破坏完全恢复了THP-1细胞中Vif缺陷型病毒的感染性。这些结果表明Vif在HIV-1在THP-1细胞中复制期间的主要功能是靶向和降解A3酶。
HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4+ T lymphocytes and macrophages. Previous studies have demonstrated that the APOBEC3 (A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4+ T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4+ T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins or has additional essential targets during viral replication is currently unknown. Herein, we describe the development and characterization of A3F-, A3F/A3G-, and A3A-to-A3G-null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and A3F-null THP-1 cells, and a more modest decrease in infectivity in A3F/A3G-null cells. Remarkably, disruption of A3A–A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during HIV-1 replication in THP-1 cells is the targeting and degradation of A3 enzymes.