DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles
Background: Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/12/12/2752 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850041241937379328 |
|---|---|
| author | Qinyi Zhang Sicong Yu Zhangnv Yang Xingxing Wang Jianhua Li Lingxuan Su Huijun Zhang Xiuyu Lou Haiyan Mao Yi Sun Lei Fang Hao Yan Yanjun Zhang |
| author_facet | Qinyi Zhang Sicong Yu Zhangnv Yang Xingxing Wang Jianhua Li Lingxuan Su Huijun Zhang Xiuyu Lou Haiyan Mao Yi Sun Lei Fang Hao Yan Yanjun Zhang |
| author_sort | Qinyi Zhang |
| collection | DOAJ |
| description | Background: Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against the virus. Methods: In this study, we investigated the role of pyroptosis in the pathogenic mechanism of dengue fever by examining the level of pyroptosis in DENV-1-infected macrophages and further screened differentially expressed microRNAs by high-throughput sequencing to predict microRNAs that could affect the pyroptosis of the macrophage. Results: Macrophages infected with DENV-1 were induced with decreased cell viability, decreased release of lactate dehydrogenase and IL-1β, activation of NLRP3 inflammasome and caspase-1, cleavage of GSDMD to produce an N-terminal fragment bound to cell membrane, and finally induced macrophage pyroptosis. MicroRNA expression profiles were obtained by sequencing macrophages from all periods of DENV-1 infection and comparing with the negative control. Sixty-three microRNAs differentially expressed in both the early and later stages of infection were also identified. In particular, miR-223-3p, miR-148a-3p, miR-125a-5p, miR-146a-5p and miR-34a-5p were recognized as small molecules that may be involved in the regulation of inflammation. Conclusions: In summary, this study aimed to understand the pathogenic mechanism of DENV through relevant molecular mechanisms and provide new targets for dengue-specific therapy. |
| format | Article |
| id | doaj-art-e6016e19133d4302b1c92582ebbbee86 |
| institution | DOAJ |
| issn | 2227-9059 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-e6016e19133d4302b1c92582ebbbee862025-08-20T02:55:49ZengMDPI AGBiomedicines2227-90592024-11-011212275210.3390/biomedicines12122752DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression ProfilesQinyi Zhang0Sicong Yu1Zhangnv Yang2Xingxing Wang3Jianhua Li4Lingxuan Su5Huijun Zhang6Xiuyu Lou7Haiyan Mao8Yi Sun9Lei Fang10Hao Yan11Yanjun Zhang12Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaInstitute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, National Human Diseases Animal Model Resource Center, Beijing 100021, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaDepartment of Critical Care Medicine, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaZhejiang Provincial Center for Disease Control and Prevention, Hangzhou 310051, ChinaBackground: Dengue virus (DENV) is the most widespread mosquito-borne virus, which can cause dengue fever with mild symptoms, or progress to fatal dengue hemorrhagic fever and dengue shock syndrome. As the main target cells of DENV, macrophages are responsible for the innate immune response against the virus. Methods: In this study, we investigated the role of pyroptosis in the pathogenic mechanism of dengue fever by examining the level of pyroptosis in DENV-1-infected macrophages and further screened differentially expressed microRNAs by high-throughput sequencing to predict microRNAs that could affect the pyroptosis of the macrophage. Results: Macrophages infected with DENV-1 were induced with decreased cell viability, decreased release of lactate dehydrogenase and IL-1β, activation of NLRP3 inflammasome and caspase-1, cleavage of GSDMD to produce an N-terminal fragment bound to cell membrane, and finally induced macrophage pyroptosis. MicroRNA expression profiles were obtained by sequencing macrophages from all periods of DENV-1 infection and comparing with the negative control. Sixty-three microRNAs differentially expressed in both the early and later stages of infection were also identified. In particular, miR-223-3p, miR-148a-3p, miR-125a-5p, miR-146a-5p and miR-34a-5p were recognized as small molecules that may be involved in the regulation of inflammation. Conclusions: In summary, this study aimed to understand the pathogenic mechanism of DENV through relevant molecular mechanisms and provide new targets for dengue-specific therapy.https://www.mdpi.com/2227-9059/12/12/2752dengue virusmacrophagespyroptosismicroRNA |
| spellingShingle | Qinyi Zhang Sicong Yu Zhangnv Yang Xingxing Wang Jianhua Li Lingxuan Su Huijun Zhang Xiuyu Lou Haiyan Mao Yi Sun Lei Fang Hao Yan Yanjun Zhang DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles Biomedicines dengue virus macrophages pyroptosis microRNA |
| title | DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles |
| title_full | DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles |
| title_fullStr | DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles |
| title_full_unstemmed | DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles |
| title_short | DENV-1 Infection of Macrophages Induces Pyroptosis and Causes Changes in MicroRNA Expression Profiles |
| title_sort | denv 1 infection of macrophages induces pyroptosis and causes changes in microrna expression profiles |
| topic | dengue virus macrophages pyroptosis microRNA |
| url | https://www.mdpi.com/2227-9059/12/12/2752 |
| work_keys_str_mv | AT qinyizhang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT sicongyu denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT zhangnvyang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT xingxingwang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT jianhuali denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT lingxuansu denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT huijunzhang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT xiuyulou denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT haiyanmao denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT yisun denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT leifang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT haoyan denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles AT yanjunzhang denv1infectionofmacrophagesinducespyroptosisandcauseschangesinmicrornaexpressionprofiles |