HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection
HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection
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DOI：
10.1016/j.virol.2012.02.002
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发表时间：
2012-05-25
期刊：
影响因子：
3.7
通讯作者：
Ratner, Lee
中科院分区：
文献类型：
--
作者：
McCulley, Anna;Ratner, Lee
HIV-2 Vpx是一种病毒相关的辅助蛋白，对于非分裂髓系细胞的感染至关重要。了解Vpx泛素化的功能。与E3泛素连接酶复合物的相互作用，以及克服逆转录抑制的能力，我们分析了Vpx赖氨酸突变体在巨噬细胞中的功能和复制能力。在HeLa细胞中，Wt Vpx和Vpx TA（lysine-less Vpx）均定位于细胞质和细胞核。所有HIV-2 Vpx赖氨酸突变体在病毒体包装中都是功能性的。然而，Vpx TA和Vpx K84 A突变体不存在泛素化，表明K68和K77位置上缺乏泛素。突变体Vpx K68 A和K77 A不能感染巨噬细胞，这是由于与泛素底物受体DCAF 1的相互作用丧失而导致逆转录受损。尽管Vpx K84 A缺乏泛素化，但它结合DCAF 1，并感染与Wt Vpx相当的巨噬细胞。(C)2012 Elsevier Inc. All rights reserved.
HIV-2 Vpx, a virus-associated accessory protein, is critical for infection of non-dividing myeloid cells. To understand the function of Vpx ubiquitination. interaction with an E3 ubiquitin ligase complex, and ability to overcome an inhibition of reverse transcription, we analyzed Vpx lysine mutants for their function and replication capability in macrophages. Both Wt Vpx and Vpx TA (lysine-less Vpx) localized to the cytoplasm and nucleus in HeLa cells. All HIV-2 Vpx lysine mutants were functional in virion packaging. However, ubiquitination was absent with Vpx TA and Vpx K84A mutants, indicating a lack of ubiquitin on positions K68 and K77. Mutants Vpx K68A and K77A were unable to infect macrophages due to impaired reverse transcription from loss of interaction with the ubiquitin substrate receptor, DCAF1. Even though Vpx K84A lacked ubiquitination, it bound DCAF1, and infected macrophages comparable to Wt Vpx. (C) 2012 Elsevier Inc. All rights reserved.