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Updated: Jun 14, 2026
Zika Virus Infectious Cell Culture System and the In Vitro Prophylactic Effect of Interferons
Published on: August 23, 2016
STAT2-dependent restriction of Zika virus by human macrophages but not dendritic cells
Dong Yang1, Hin Chu1, Gang Lu2,3,4
1State Key Laboratory of Emerging Infectious Diseases, Department of Microbiology, The University of Hong Kong, Pokfulam, People's Republic of China.
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.
Insights
Macrophages restrict Zika virus (ZIKV) replication by maintaining type I interferon responses, unlike dendritic cells which support ZIKV infection and apoptosis. This highlights differential immune cell roles in flavivirus pathogenesis.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Zika virus (ZIKV) is a significant public health threat, transmitted by mosquitoes.
- Macrophages and dendritic cells are crucial immune sentinels in flavivirus infections.
- ZIKV infects dendritic cells, but its interaction with macrophages is less understood.
Purpose of the Study:
- To compare Zika virus infection and replication in monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (moDCs).
- To elucidate the mechanisms underlying differential ZIKV interactions with these myeloid cells.
- To investigate the role of STAT signaling in ZIKV restriction by macrophages.
Main Methods:
- Comparison of ZIKV susceptibility and replication in MDMs and moDCs from the same donors.
- Analysis of ZIKV-induced apoptosis in MDMs and moDCs.
- Assessment of viral entry, STAT1/STAT2 phosphorylation, and type I interferon responses.
- Gene depletion studies (STAT2, STAT1) to assess their role in ZIKV replication.
Main Results:
- Both MDMs and moDCs were susceptible to ZIKV, but replication was restricted in MDMs.
- ZIKV induced apoptosis in moDCs but not MDMs.
- ZIKV failed to inhibit STAT1/STAT2 phosphorylation in MDMs, preserving type I interferon responses.
- STAT2 depletion in MDMs rescued ZIKV replication, indicating its role in viral restriction.
Conclusions:
- Macrophages restrict ZIKV infection through intact STAT-mediated type I interferon signaling.
- Dendritic cells are productively infected by ZIKV, leading to apoptosis and potentially facilitating viral spread.
- This study reveals distinct roles for macrophages and dendritic cells in ZIKV pathogenesis.
