Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function

Huang, Yutian; Liu, Yuwei; Li, Rongrong; Zhu, Xi; Li, Ruidong; Peng, Sihao; An, Xin; Yang, Yuxin; Liu, Yuanyuan; Wen, Yiping; Zhao, Qin; Zhao, Shan; Zhao, Fei; Wu, Rui; Huang, Xiaobo; Yan, Qigui; Lang, Yifei; Wang, Yiping; Hu, Yajie; Zheng, Yi; Cao, Sanjie; Du, Senyan

doi:10.3390/ijms262311727

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Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function

by

Yutian Huang

^1,†

,

Yuwei Liu

^1,†,

Rongrong Li

¹,

Xi Zhu

¹,

Ruidong Li

¹,

Sihao Peng

¹,

Xin An

¹,

Yuxin Yang

¹,

Yuanyuan Liu

¹,

Yiping Wen

^1,2,3,4,

Qin Zhao

^1,2,3,4

,

Shan Zhao

^1,2,3,4,

Fei Zhao

^1,2,3,4,

Rui Wu

^1,2,3,4

,

Xiaobo Huang

^1,2,3,4,

Qigui Yan

^1,2,3,4,

Yifei Lang

^1,2,3,4,

Yiping Wang

^1,2,3,4,

Yajie Hu

⁵,

Yi Zheng

^1,2,3,4,

Sanjie Cao

^1,2,3,4

and

Senyan Du

^1,2,3,4,* Show full author list Hide full author list

¹

Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China

²

Sichuan Science-Observation Experimental Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu 611130, China

³

Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People’s Republic of China, Chengdu 611130, China

⁴

Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China

⁵

Sichuan Center for Disease Control and Prevention, Chengdu 610041, China

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(23), 11727; https://doi.org/10.3390/ijms262311727

Submission received: 7 October 2025 / Revised: 27 November 2025 / Accepted: 1 December 2025 / Published: 3 December 2025

(This article belongs to the Special Issue Investigating Host-Parasite Interactions for the Discovery of Novel Therapies and Vaccine Targets)

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Abstract

Thioester-containing proteins (TEPs), which are distinguished by the thioester motif (GCGEQ), are essential to arthropods’ defense against infections. Although TEPs have been extensively investigated in Anopheles, Aedes, and Drosophila, their functions in Culex mosquitoes remain inadequately explored. Interestingly, we discovered that Culex TEPs exhibit functional antagonism to their orthologs in other species, actively facilitating viral infection in this vector. In this study, we identified nine TEP genes in Culex quinquefasciatus, three of which were found to critically facilitate Japanese encephalitis virus (JEV) infection, with CqTEP27 exhibiting the most pronounced proviral effect. Mechanistically, CqTEP27 may have suppressed the production of several antimicrobial peptides (AMPs), which increased JEV replication. Our work also highlights the potential of targeting susceptibility factors such as CqTEP27 to block pathogen acquisition. Notably, the rate of mosquito infection was significantly decreased by membrane blood feeding antisera against CqTEP27. Therefore, vaccination against CqTEP27 offers a workable method of avoiding JEV infection. According to our research, CqTEP27 is a promising target for the development of vaccines that prevent JEV transmission. By preventing viral infection in mosquitoes that feed on immunized hosts, this approach can directly disrupt the natural transmission cycle, offering a novel strategy to reduce the disease burden.

Keywords: Culex quinquefasciatus; thioester-containing protein (TEP); Japanese encephalitis virus; innate immunity; antimicrobial peptides

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MDPI and ACS Style

Huang, Y.; Liu, Y.; Li, R.; Zhu, X.; Li, R.; Peng, S.; An, X.; Yang, Y.; Liu, Y.; Wen, Y.; et al. Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function. Int. J. Mol. Sci. 2025, 26, 11727. https://doi.org/10.3390/ijms262311727

AMA Style

Huang Y, Liu Y, Li R, Zhu X, Li R, Peng S, An X, Yang Y, Liu Y, Wen Y, et al. Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function. International Journal of Molecular Sciences. 2025; 26(23):11727. https://doi.org/10.3390/ijms262311727

Chicago/Turabian Style

Huang, Yutian, Yuwei Liu, Rongrong Li, Xi Zhu, Ruidong Li, Sihao Peng, Xin An, Yuxin Yang, Yuanyuan Liu, Yiping Wen, and et al. 2025. "Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function" International Journal of Molecular Sciences 26, no. 23: 11727. https://doi.org/10.3390/ijms262311727

APA Style

Huang, Y., Liu, Y., Li, R., Zhu, X., Li, R., Peng, S., An, X., Yang, Y., Liu, Y., Wen, Y., Zhao, Q., Zhao, S., Zhao, F., Wu, R., Huang, X., Yan, Q., Lang, Y., Wang, Y., Hu, Y., ... Du, S. (2025). Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function. International Journal of Molecular Sciences, 26(23), 11727. https://doi.org/10.3390/ijms262311727

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Thioester-Containing Protein TEP27 in Culex quinquefasciatus Promotes JEV Infection by Modulating Host Immune Function

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