SGK1, a Serine/Threonine Kinase, Inhibits Prototype Foamy Virus Replication.
SGK1, a Serine/Threonine Kinase, Inhibits Prototype Foamy Virus Replication.
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SGK1，一种丝氨酸/苏氨酸激酶，抑制原型泡沫病毒复制
DOI：
10.1128/spectrum.01995-21
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发表时间：
2022-06-29
影响因子：
3.7
通讯作者：
Tan, Juan
中科院分区：
文献类型：
--
作者：
Zhang, Junshi;Han, Chunhua;Xiong, Zhenjie;Qiu, Manman;Tuo, Xiaopeng;Wang, Chenchen;Qiao, Wentao;Tan, Juan
泡沫病毒是一种复杂的逆转录病毒，属于逆转录病毒科的泡沫逆转录病毒亚科。与逆转录病毒科的另一个成员人类免疫缺陷病毒（HIV）相反，FV在其天然宿主或实验感染的动物中是非致病性的。原型泡沫病毒（Prototype foamy virus，PFV）是唯一一种可以通过跨种属传播感染人类，且感染后不显示任何致病性的泡沫病毒。因此，PFV被认为是一种安全有效的基因转移载体。了解参与PFV复制的宿主蛋白以及宿主与病毒之间相互作用的机制可能会导致研究以提高基因转移的效率。迄今为止，只有少数宿主因素已被确定影响PFV复制。在本研究中，我们报告PFV感染增强SGK 1（编码血清/糖皮质激素调节激酶1）的启动子活性通过Tas蛋白信号通路，然后上调SGK 1的mRNA和蛋白水平。SGK 1的过表达减少PFV复制，而其使用小干扰RNA消耗增加PFV复制。SGK 1通过以非激酶依赖性方式损害PFV Tas激活结构域的功能并以激酶依赖性方式降低Gag蛋白的稳定性来抑制PFV复制。此外，人和牛SGK 1蛋白都抑制牛泡沫病毒（BFV）和PFV的复制。这些发现不仅加深了我们对SGK 1功能及其与泡沫病毒关系的理解，而且有助于确定宿主的抗病毒机制。泡沫病毒可以整合到宿主染色体中，在自然宿主或实验感染的动物中是非致病性的。因此，泡沫病毒被认为是安全有效的基因转移载体。泡沫病毒的持续感染部分是由于宿主因素对病毒的限制作用所致。然而，已知只有少数细胞蛋白质影响泡沫病毒的复制。在这项研究中，我们报告说，SGK 1抑制原型泡沫病毒的复制，通过影响转录激活因子，Tas的功能，并降低结构蛋白，Gag的稳定性。这些结果将增加我们对病毒与宿主因子之间相互作用的理解，加深我们对宿主抗病毒防御和SGK 1功能的认识，并可能提高泡沫病毒的基因转移效率。
Foamy viruses (FVs) are complex retroviruses belonging to the Spumaretrovirinae subfamily of the Retroviridae family. In contrast to human immunodeficiency virus (HIV), another member of the Retroviridae family, FVs are nonpathogenic in their natural hosts or in experimentally infected animals. Prototype foamy virus (PFV) is the only foamy virus that can infect humans through cross-species transmission and does not show any pathogenicity after infection. Consequently, PFV is considered a safe and efficient gene transfer vector. Understanding the host proteins involved in the replication of PFV and the mechanism of interaction between the host and the virus might lead to studies to improve the efficiency of gene transfer. To date, only a few host factors have been identified that affect PFV replication. In the present study, we report that PFV infection enhances the promoter activity of SGK1 (encoding serum/glucocorticoid regulated kinase 1) via the Tas protein signaling pathway, and then upregulates the mRNA and protein levels of SGK1. Overexpression of SGK1 reduced PFV replication, whereas its depletion using small interfering RNA increased PFV replication. SGK1 inhibits PFV replication by impairing the function of the PFV Tas activation domain in a kinase-independent manner and reducing the stability of the Gag protein in a kinase-dependent manner. In addition, both human and bovine SGK1 proteins inhibit the replication of bovine foamy virus (BFV) and PFV. These findings not only improved our understanding of the function of SGK1 and its relationship with foamy viruses, but also contributed to determining the antiviral mechanism of the host. IMPORTANCE Foamy viruses can integrate into the host chromosome and are nonpathogenic in natural hosts or in experimentally infected animals. Therefore, foamy viruses are considered to be safe and efficient gene transfer vectors. Persistent infection of foamy viruses is partly caused by the restrictive effect of host factors on the virus. However, only a few cellular proteins are known to influence the replication of foamy viruses. In this study, we report that SGK1 inhibits the replication of prototype foamy virus by affecting the function of the transcription activator, Tas, and reducing the stability of the structural protein, Gag. These results will increase our understanding of the interaction between the virus and host factors, deepening our perception of host antiviral defenses and the function of SGK1, and could improve the gene transfer efficiency of foamy viruses.
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影响因子：
32.4
作者：
Blanco-Melo D;Venkatesh S;Bieniasz PD
通讯作者：
Bieniasz PD
影响因子：
5.5
作者：
Bing, Tiejun;Yu, Hong;Qiao, Wentao
通讯作者：
Qiao, Wentao
影响因子：
5.2
作者：
Bodem, J;Lochelt, M;Flugel, RM
通讯作者：
Flugel, RM
影响因子：
9.2
作者：
Casamayor, A;Torrance, PD;Alessi, DR
通讯作者：
Alessi, DR
影响因子：
5.4
作者：
CHANG, J;LEE, KJ;SUNG, YC
通讯作者：
SUNG, YC