Adaptor protein complex 1 gamma 1 subunit is an important host factor involved in both Zika virus and dengue virus infections

Jinna Yang; Changbai Huang; Yao Feng; Junfang He; Yang Liu; Ping Zhang; Chao Liu

doi:10.1016/j.virs.2025.07.012

December 2025

Citation: Jinna Yang, Changbai Huang, Yao Feng, Junfang He, Yang Liu, Ping Zhang, Chao Liu. Adaptor protein complex 1 gamma 1 subunit is an important host factor involved in both Zika virus and dengue virus infections .VIROLOGICA SINICA, 2025, 40(6) : 874-883. http://dx.doi.org/10.1016/j.virs.2025.07.012

Adaptor protein complex 1 gamma 1 subunit is an important host factor involved in both Zika virus and dengue virus infections

Jinna Yang ^a,b ,
Changbai Huang ^a,b ,
Yao Feng ^a,b ,
Junfang He ^a,b ,
Yang Liu ^c ,
Ping Zhang ^{a,b
,,} ,
Chao Liu ^{a,b
,,}

a. Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Guangzhou, 510080, China;
b. Department of Immunology and Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China;
c. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, 999077, China

Corresponding author: Ping Zhang, zhangp36@mail.sysu.edu.cn
Chao Liu, liuchao9@mail.sysu.edu.cn
Received Date: 19 March 2025
Accepted Date: 30 July 2025
Available online: 05 August 2025

Abstract

Mosquito-borne flaviviruses, such as Zika virus (ZIKV) and dengue virus (DENV), cause diverse severe clinical manifestations including fever, rash, hepatitis, arthralgia, and congenital anomalies. Here, we identified a host factor, the adaptor protein complex 1 gamma 1 subunit (AP1G1), which plays an important role in both ZIKV and dengue virus 2 (DENV2) infections. We explored the role of AP1G1 in ZIKV and DENV2 infections using CRISPR/Cas9 gene editing technology and RNA interference (RNAi) techniques. Knockout or silencing of AP1G1 decreases the replication of ZIKV and DENV2 in multiple human cell lines. Intriguingly, depletion of AP1G1 results in a significant reduction in ZIKV at an early stage, but decreases DENV2 replication levels during the late stage, suggesting that AP1G1 plays distinct roles in the infection by ZIKV and DENV2. Furthermore, we determined that AP1G1 mediates ZIKV-endosomal membrane fusion through inhibitor experiments and fluorescence labeling assays. Mechanistically, we found that AP1G1 exerts its pro-viral effect through binding to the ZIKV envelope glycoprotein (E protein). This interaction promotes the fusion of viral and endosomal membranes, during which the ZIKV genomic RNAs are released from the endosome into the cytoplasm, a process that facilitates viral replication. However, for DENV2 infection, AP1G1 primarily affects its viral RNA replication stage, rather than the fusion of virus-endosomal membrane. Taken together, our work demonstrates that AP1G1 plays a pro-viral role in both ZIKV and DENV2 infections via distinct mechanisms, highlighting its potential as a therapeutic target for antiviral strategies.
- Zika virus (ZIKV)
- , Dengue virus (DENV)
- , Adaptor protein complex 1 gamma 1 subunit (AP1G1)
- , Endosome

Electronic Supplementary Material

10.1016j.virs.2025.07.012.docx
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