GTPase Activity of MxB Contributes to Its Nuclear Location, Interaction with Nucleoporins and Anti-HIV-1 Activity
GTPase Activity of MxB Contributes to Its Nuclear Location, Interaction with Nucleoporins and Anti-HIV-1 Activity
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MxB 的 GTP 酶活性有助于其核定位、与核孔蛋白的相互作用以及抗 HIV-1 活性
DOI：
10.1007/s12250-020-00249-8
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发表时间：
2020-07-06
影响因子：
5.5
通讯作者：
Feng, Yong
中科院分区：
文献类型：
--
作者：
Xie, Linlin;Ju, Zhao;Feng, Yong
人粘病毒抗性2（Mx2/MxB）蛋白是干扰素（IFN）诱导的动力蛋白样大GTP酶的成员，限制了许多病毒感染。这些病毒的抑制发生在病毒进入后的定义不明确的步骤，并具有MxB寡聚化的共同要求。然而，GTdR活性对于MxB抗疱疹病毒和HBV的抗病毒作用是必需的，但对HIV-1不是。为了了解MxB GTP酶活性（包括GTP结合和GTP水解）在限制HIV-1感染中的作用，我们从遗传学上分离了这两种功能，并评估了它们对限制的贡献。我们发现MxB的GTP结合和水解功能参与了HIV-1复制的限制。MxB的GTP酶活性与其核定位、与核孔蛋白（NUPs）和HIV-1衣壳的相互作用有关。此外，MxB破坏NUPs和HIV-1核心之间的关联依赖于其GT3活性。因此，GT3活性的功能是多方面的，导致野生型MxB和GT3活性缺陷型MxB突变所采用的基本上不同的机制来限制HIV-1复制。
The human myxovirus resistance 2 (Mx2/MxB) protein, a member of interferon (IFN)-inducible dynamin-like large GTPases, restricts a number of virus infections. Inhibition of these viruses occurs at poorly-defined steps after viral entry and has a common requirement for MxB oligomerization. However, the GTPase activity is essential for the anti-viral effects of MxB against herpesviruses and HBV but not HIV-1. To understand the role of MxB GTPase activity, including GTP binding and GTP hydrolysis, in restriction of HIV-1 infection, we genetically separated these two functions and evaluated their contributions to restriction. We found that both the GTP binding and hydrolysis function of MxB involved in the restriction of HIV-1 replication. The GTPase activity of MxB contributed to its nuclear location, interaction with nucleoporins (NUPs) and HIV-1 capsids. Furthermore, MxB disrupted the association between NUPs and HIV-1 cores dependently upon its GTPase activity. The function of GTPase activity was therefore multi-faceted, led to fundamentally distinct mechanisms employed by wild-type MxB and GTPase activity defective MxB mutations to restrict HIV-1 replication.