Ectromelia virus upregulates the expression of heat shock protein 70 to promote viral replication

文献类型： 外文期刊

第一作者： Cheng, Wenyu

作者： Cheng, Wenyu;Jia, Huaijie;Wang, Xiaoxia;He, Xiaobing;Jin, Qiwang;Jing, Zhizhong;Cheng, Wenyu;Wang, Xiaoxia;Cao, Jingxin

作者机构：

关键词： ectromelia virus; Hspa1b; small-molecule inhibitor; viral replication

期刊名称：INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE （ 影响因子：4.101； 五年影响因子：4.084 ）

ISSN： 1107-3756

年卷期： 2018 年 42 卷 2 期

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收录情况： SCI

摘要： The ectromelia virus (ECTV) is a mouse specific Orthopoxvirus that causes lethal infection in some mouse strains. ECTV infection of these mouse strains has been used as a valuable model for understanding the interplay between Orthopoxvirus species and their hosts, including variola virus in humans. Although poxviruses encode numerous proteins required for DNA and RNA synthesis, and are less dependent on host functions than other DNA viruses, a detailed understanding of the host factors required for the replication of poxviruses is lacking. Heat shock protein 70 (Hsp70) isoforms have been reported to serve various roles in the replication cycle of numerous viruses. In the present study, microarray and reverse transcription-quantitative polymerase chain reaction analysis were conducted to investigate the host gene expression profiles following ECTV infection in mice and cell cultures. The results indicated that one Hsp70 isoform, Hsp70 member 1B (Hspa1b), was highly upregulated during ECTV infection in vitro and in vivo. Subsequently, overexpression of Hspa1b protein and small interfering RNA-mediated gene silencing of Hspa1b revealed that Hspa1b is required for efficient replication of ECTV. Furthermore, the results demonstrated that ECTV replication may be significantly suppressed by two chemical Hspa1b inhibitors: Quercetin and VER155008. In conclusion, the present study clearly demonstrated that ECTV infection upregulates the expression of Hspa1b in order to promote its replication. The dependence on Hsp70 may be used as a novel therapeutic target for the treatment of Orthopoxvirus infection.

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