Targeting conserved co-opted host factors to block virus replication: Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication
Targeting conserved co-opted host factors to block virus replication: Using allosteric inhibitors of the cytosolic Hsp70s to interfere with tomato bushy stunt virus replication
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DOI：
10.1016/j.virol.2021.08.002
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发表时间：
2021-08-13
期刊：
影响因子：
3.7
通讯作者：
Nagy，Peter D.
中科院分区：
文献类型：
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作者：
Molho，Melissa;Prasanth，K. Reddisiva;Nagy，Peter D.
为了进一步了解宿主胞质热休克蛋白70 （Hsp70）家族的前病毒作用，我们选择了保守的darabidopsis thalianaHsp70-2和独特的Erd2（早期脱水反应2），它们含有Hsp70结构域。基于纯化组分的onin体外研究，我们发现AtHsp70-2和AtErd2具有与酵母Ssa1 Hsp70相同的前病毒功能。这些功能包括激活瘤状病毒RdRp和刺激复制酶组装。基于酵母的互补研究表明，纯化的瘤病毒复制酶中存在AtHsp70-2或AtErd2。研究表明，Hsp70-2和Erd2均可被番茄丛矮病毒（TBSV）吸收。此外，我们使用hsp70的变构抑制剂来抑制TBSV和相关植物病毒在植物中的复制。总之，干扰增选的hsp70的功能可能是一种有效的抗病毒方法。
To further our understanding of the pro-viral roles of the host cytosolic heat shock protein 70 (Hsp70) family, we chose the conservedArabidopsis thalianaHsp70-2 and the unique Erd2 (early response to dehydration 2), which contain Hsp70 domains. Based onin vitrostudies with purified components, we show that AtHsp70-2 and AtErd2 perform pro-viral functions equivalent to that of the yeast Ssa1 Hsp70. These functions include activation of the tombusvirus RdRp, and stimulation of replicase assembly. Yeast-based complementation studies demonstrate that AtHsp70-2 or AtErd2 are present in the purified tombusvirus replicase. RNA silencing and over-expression studies inNicotiana benthamianasuggest that both Hsp70-2 and Erd2 are co-opted by tomato bushy stunt virus (TBSV). Moreover, we used allosteric inhibitors of Hsp70s to inhibit replication of TBSV and related plant viruses in plants. Altogether, interfering with the functions of the co-opted Hsp70s could be an effective antiviral approach against tombusviruses in plants.