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Article: STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells
Title | STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells |
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Authors | |
Keywords | Dendritic cells flavivirus macrophages interferon signaling STAT1 |
Issue Date | 2021 |
Publisher | Taylor & Francis, published in association with Shanghai Shangyixun Cultural Communication Company. The Journal's web site is located at https://www.tandfonline.com/toc/temi20/current |
Citation | Emerging Microbes & Infections, 2021, v. 10 n. 1, p. 1024-1037 How to Cite? |
Abstract | Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that poses significant threats to global public health. Macrophages and dendritic cells are both key sentinel cells in the host immune response and play critical roles in the pathogenesis of flavivirus infections. Recent studies showed that ZIKV could productively infect monocyte-derived dendritic cells (moDCs), but the role of macrophages in ZIKV infection remains incompletely understood. In this study, we first compared ZIKV infection in monocyte-derived macrophages (MDMs) and moDCs derived from the same donors. We demonstrated that while both MDMs and moDCs were susceptible to epidemic (Puerto Rico) and pre-epidemic (Uganda) strains of ZIKV, virus replication was largely restricted in MDMs but not in moDCs. ZIKV induced significant apoptosis in moDCs but not MDMs. The restricted virus replication in MDMs was not due to inefficient virus entry but was related to post-entry events in the viral replication cycle. In stark contrast with moDCs, ZIKV failed to inhibit STAT1 and STAT2 phosphorylation in MDMs. This resulted in the lack of efficient antagonism of the host type I interferon-mediated antiviral responses. Importantly, depletion of STAT2 but not STAT1 in MDMs significantly rescued the replication of ZIKV and the prototype flavivirus yellow fever virus. Overall, our findings revealed a differential interplay between macrophages and dendritic cells with ZIKV. While dendritic cells may be exploited by ZIKV to facilitate virus replication, macrophages restricted ZIKV infection. |
Persistent Identifier | http://hdl.handle.net/10722/310128 |
ISSN | 2023 Impact Factor: 8.4 2023 SCImago Journal Rankings: 2.316 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yang, D | - |
dc.contributor.author | Chu, H | - |
dc.contributor.author | Lu, G | - |
dc.contributor.author | Shuai, H | - |
dc.contributor.author | Wang, Y | - |
dc.contributor.author | Hou, Y | - |
dc.contributor.author | Zhang, X | - |
dc.contributor.author | Huang, X | - |
dc.contributor.author | Hu, B | - |
dc.contributor.author | Chai, Y | - |
dc.contributor.author | Yuen, TTT | - |
dc.contributor.author | Zhao, X | - |
dc.contributor.author | Lee, ACY | - |
dc.contributor.author | Ye, Z | - |
dc.contributor.author | Li, C | - |
dc.contributor.author | Chik, KKH | - |
dc.contributor.author | Zhang, AJ | - |
dc.contributor.author | Zhou, J | - |
dc.contributor.author | Yuan, S | - |
dc.contributor.author | Chan, JFW | - |
dc.date.accessioned | 2022-01-24T02:24:15Z | - |
dc.date.available | 2022-01-24T02:24:15Z | - |
dc.date.issued | 2021 | - |
dc.identifier.citation | Emerging Microbes & Infections, 2021, v. 10 n. 1, p. 1024-1037 | - |
dc.identifier.issn | 2222-1751 | - |
dc.identifier.uri | http://hdl.handle.net/10722/310128 | - |
dc.description.abstract | Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that poses significant threats to global public health. Macrophages and dendritic cells are both key sentinel cells in the host immune response and play critical roles in the pathogenesis of flavivirus infections. Recent studies showed that ZIKV could productively infect monocyte-derived dendritic cells (moDCs), but the role of macrophages in ZIKV infection remains incompletely understood. In this study, we first compared ZIKV infection in monocyte-derived macrophages (MDMs) and moDCs derived from the same donors. We demonstrated that while both MDMs and moDCs were susceptible to epidemic (Puerto Rico) and pre-epidemic (Uganda) strains of ZIKV, virus replication was largely restricted in MDMs but not in moDCs. ZIKV induced significant apoptosis in moDCs but not MDMs. The restricted virus replication in MDMs was not due to inefficient virus entry but was related to post-entry events in the viral replication cycle. In stark contrast with moDCs, ZIKV failed to inhibit STAT1 and STAT2 phosphorylation in MDMs. This resulted in the lack of efficient antagonism of the host type I interferon-mediated antiviral responses. Importantly, depletion of STAT2 but not STAT1 in MDMs significantly rescued the replication of ZIKV and the prototype flavivirus yellow fever virus. Overall, our findings revealed a differential interplay between macrophages and dendritic cells with ZIKV. While dendritic cells may be exploited by ZIKV to facilitate virus replication, macrophages restricted ZIKV infection. | - |
dc.language | eng | - |
dc.publisher | Taylor & Francis, published in association with Shanghai Shangyixun Cultural Communication Company. The Journal's web site is located at https://www.tandfonline.com/toc/temi20/current | - |
dc.relation.ispartof | Emerging Microbes & Infections | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | Dendritic cells | - |
dc.subject | flavivirus | - |
dc.subject | macrophages | - |
dc.subject | interferon signaling | - |
dc.subject | STAT1 | - |
dc.title | STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells | - |
dc.type | Article | - |
dc.identifier.email | Chu, H: hinchu@hku.hk | - |
dc.identifier.email | Shuai, H: shuaihp@connect.hku.hk | - |
dc.identifier.authority | Chu, H=rp02125 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1080/22221751.2021.1929503 | - |
dc.identifier.pmid | 33979266 | - |
dc.identifier.pmcid | PMC8205058 | - |
dc.identifier.scopus | eid_2-s2.0-85107792243 | - |
dc.identifier.hkuros | 331495 | - |
dc.identifier.volume | 10 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | 1024 | - |
dc.identifier.epage | 1037 | - |
dc.identifier.isi | WOS:000658884500001 | - |
dc.publisher.place | United Kingdom | - |