Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins.
Strain-Dependent Restriction of Human Cytomegalovirus by Zinc Finger Antiviral Proteins.
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锌指抗病毒蛋白对人巨细胞病毒的菌株依赖性限制。
DOI：
10.1128/jvi.01846-22
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发表时间：
2023-03-30
影响因子：
5.4
通讯作者：
Strang, Blair L.
中科院分区：
文献类型：
--
作者：
Lista, Maria Jose;Witney, Adam A.;Nichols, Jenna;Davison, Andrew J.;Wilson, Harry;Latham, Katie A.;Ravenhill, Benjamin J.;Nightingale, Katie;Stanton, Richard J.;Weekes, Michael P.;Neil, Stuart J. D.;Swanson, Chad M.;Strang, Blair L.
识别病毒核酸的细胞抗病毒因子可以抑制病毒复制。这些包括锌指抗病毒蛋白（ZAP），其识别病毒RNA中的高CpG二核苷酸含量。在这里，我们研究了ZAP抑制人巨细胞病毒（HCMV）复制的能力。ZAP或其辅因子KHNYN的消耗增加了高传代HCMV株AD 169的滴度，但对低传代株Merlin的滴度几乎没有影响。我们发现在ZAP敲减细胞中，AD169和Merlin之间的几种病毒蛋白的表达没有明显差异，但是在不存在ZAP的情况下，与Merlin相比，在AD169中观察到感染性病毒的更大增加，这表明ZAP抑制了AD169复制后期的事件。此外，AD169和Merlin RNA的CpG丰度没有明显差异，表明两种病毒株的基因组含量不太可能是它们对ZAP敏感性差异的原因。相反，我们观察到在复制后期Merlin感染的细胞中ZAP表达低于AD 169感染的细胞，这可能与两种病毒株调节干扰素信号传导的能力不同有关。因此，HCMV对ZAP的敏感性存在菌株依赖性差异，低传代HCMV菌株Merlin逃避ZAP抑制的能力可能与其调节干扰素信号传导的能力有关，而不是其基因组产生的RNA的CpG含量。确定细胞抗病毒因子的功能可以帮助我们了解病毒的复制。锌指抗病毒蛋白（ZAP）可以抑制多种病毒的复制。在这里，我们研究了ZAP与DNA病毒人巨细胞病毒（HCMV）的相互作用。我们发现ZAP影响HCMV复制的能力存在HCMV毒株依赖性差异，这可能与HCMV毒株与I型干扰素系统的相互作用有关。这些观察影响了我们目前对ZAP如何限制HCMV以及HCMV如何与I型干扰素系统相互作用的理解。
Cellular antiviral factors that recognize viral nucleic acid can inhibit virus replication. These include the zinc finger antiviral protein (ZAP), which recognizes high CpG dinucleotide content in viral RNA. Here, we investigated the ability of ZAP to inhibit the replication of human cytomegalovirus (HCMV). Depletion of ZAP or its cofactor KHNYN increased the titer of the high-passage HCMV strain AD169 but had little effect on the titer of the low-passage strain Merlin. We found no obvious difference in expression of several viral proteins between AD169 and Merlin in ZAP knockdown cells, but observed a larger increase in infectious virus in AD169 compared to Merlin in the absence of ZAP, suggesting that ZAP inhibited events late in AD169 replication. In addition, there was no clear difference in the CpG abundance of AD169 and Merlin RNAs, indicating that genomic content of the two virus strains was unlikely to be responsible for differences in their sensitivity to ZAP. Instead, we observed less ZAP expression in Merlin-infected cells late in replication compared to AD169-infected cells, which may be related to different abilities of the two virus strains to regulate interferon signaling. Therefore, there are strain-dependent differences in the sensitivity of HCMV to ZAP, and the ability of low-passage HCMV strain Merlin to evade inhibition by ZAP is likely related to its ability to regulate interferon signaling, not the CpG content of RNAs produced from its genome. IMPORTANCE Determining the function of cellular antiviral factors can inform our understanding of virus replication. The zinc finger antiviral protein (ZAP) can inhibit the replication of diverse viruses. Here, we examined ZAP interaction with the DNA virus human cytomegalovirus (HCMV). We found HCMV strain-dependent differences in the ability of ZAP to influence HCMV replication, which may be related to the interaction of HCMV strains with the type I interferon system. These observations affect our current understanding of how ZAP restricts HCMV and how HCMV interacts with the type I interferon system.
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影响因子：
6.7
作者：
Chiu HP;Chiu H;Yang CF;Lee YL;Chiu FL;Kuo HC;Lin RJ;Lin YL
通讯作者：
Lin YL
影响因子：
6.7
作者：
Gonçalves-Carneiro D;Takata MA;Ong H;Shilton A;Bieniasz PD
通讯作者：
Bieniasz PD
DOI：
10.1073/pnas.1302564110
发表时间：
2013-07-02
影响因子：
11.1
作者：
Charron, Guillaume;Li, Melody M. H.;Hang, Howard C.
通讯作者：
Hang, Howard C.
ZAP N 端结构域的结构表明锌指蛋白如何识别复杂的 RNA
影响因子：
16.8
作者：
Chen, Shoudeng;Xu, Yihui;Liu, Yingfang
通讯作者：
Liu, Yingfang
影响因子：
7.7
作者：
Fros JJ;Dietrich I;Alshaikhahmed K;Passchier TC;Evans DJ;Simmonds P
通讯作者：
Simmonds P