Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection
文献类型：期刊论文
| 作者 | Zhang, Lei-Ke2; Wang, Bo1,2; Xin, Qilin2; Shang, Weijuan2; Shen, Shu2; Xiao, Gengfu2; Deng, Fei2; Wang, Hualin2; Hu, Zhihong2; Wang, Manli2 |
| 刊名 | JOURNAL OF VIROLOGY
 |
| 出版日期 | 2019-05-01 |
| 卷号 | 93期号:10页码:17 |
| 关键词 | ATF6 ER stress PERK SFTSV XBP1 quantitative proteomics unfolded-protein response virus-host interaction |
| ISSN号 | 0022-538X |
| DOI | 10.1128/JVI.00308-19 |
| 英文摘要 | Severe fever with thrombocytopenia syndrome (SFTS) is an emerging, highly pathogenic, infectious disease caused by infection with a newly discovered tick-borne phlebovirus, SFTS virus (SFTSV). Limited information on the molecular mechanism of SFTSV infection and pathogenesis impedes the development of effective vaccines and drugs for SFTS prevention and treatment. In this study, an isobaric tag for relative and absolute quantification (iTRAQ)-based quantitative proteomic analysis of SFTSV-infected HEK 293 cells was performed to explore dynamic host cellular protein responses toward SFTSV infection. A total of 433 of 5,606 host proteins involved in different biological processes were differentially regulated by SFTSV infection. The proteomic results highlighted a potential role of endoplasmic reticular stress-triggered unfolded-protein response (UPR) in SFTSV infection. Further functional studies confirmed that all three major branches of the UPR, including the PKR-like endoplasmic reticulum kinase (PERK), the activating transcription factor-6 (ATF6), and the inositol-requiring protein-1 (IRE1)/X-box-binding protein 1 (XBP1) pathways, were activated by SFTSV. However, only the former two pathways play a crucial role in SFTSV infection. Furthermore, expression of SFTSV glycoprotein (GP) alone was sufficient to stimulate the UPR, whereas suppression of PERK and ATF6 notably decreased GP expression. Interestingly, two other newly discovered phleboviruses, Heartland virus and Guertu virus, also stimulated the UPR, suggesting a common mechanism shared by these genetically related phleboviruses. This study provides a global view to our knowledge on how host cells respond to SFTSV infection and highlights that host cell UPR plays an important role in phlebovirus infection. IMPORTANCE Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes severe fever with thrombocytopenia syndrome in humans, with a mortality rate reaching up to 30% in some outbreaks. There are currently no U.S. Food and Drug Administration-approved vaccines or specific antivirals available against SFTSV. To comprehensively understand the molecular interactions occurring between SFTSV and the host cell, we exploit quantitative proteomic approach to investigate the dynamic host cellular responses to SFTSV infection. The results highlight multiple biological processes being regulated by SFTSV infection. Among these, we focused on exploration of the mechanism of how SFTSV infection stimulates the host cell's unfolded-protein response (UPR) and identified the UPR as a common feature shared by SFTSV-related new emerging phleboviruses. This study, for the first time to our knowledge, provides a global map for host cellular responses to SFTSV infection and highlighted potential host targets for further research. |
| 资助项目 | National Natural Science Foundation of China[31621061] ; National Key R&D Program of China[2016YFC1200400] ; Youth Innovation Promotion Association CAS[2018367] ; Youth Innovation Promotion Association CAS[2013219] |
| WOS研究方向 | Virology |
| 语种 | 英语 |
| WOS记录号 | WOS:000466417500011 |
| 出版者 | AMER SOC MICROBIOLOGY |
| 源URL | [http://202.127.146.157/handle/2RYDP1HH/7732]  |
| 专题 | 中国科学院武汉植物园 |
| 通讯作者 | Hu, Zhihong; Wang, Manli |
| 作者单位 | 1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Wuhan Inst Virol, State Key Lab Virol, Wuhan, Hubei, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Lei-Ke,Wang, Bo,Xin, Qilin,et al. Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection[J]. JOURNAL OF VIROLOGY,2019,93(10):17. |
| APA | Zhang, Lei-Ke.,Wang, Bo.,Xin, Qilin.,Shang, Weijuan.,Shen, Shu.,...&Wang, Manli.(2019).Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection.JOURNAL OF VIROLOGY,93(10),17. |
| MLA | Zhang, Lei-Ke,et al."Quantitative Proteomic Analysis Reveals Unfolded-Protein Response Involved in Severe Fever with Thrombocytopenia Syndrome Virus Infection".JOURNAL OF VIROLOGY 93.10(2019):17. |
入库方式： OAI收割
来源：武汉植物园
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