The Role of Wolbachia in DENV Replication as Dengue Control Strategies

Joy Aurel Prudentia Putri, Angelina Vivi Maharani, Condoleezza Betzy Kasi, Loury Priskila, Justinus Agung Putranto Nugroho

Abstract

Dengue fever (DHF) remains a major public health problem in tropical countries such as Indonesia, with cases continuing to rise in recent years. Conventional vector control strategies are often less effective, creating the need for innovative biotechnology-based approaches. One promising strategy is the utilization of Wolbachia bacteria, which has been shown to suppress dengue virus (DENV) replication in Aedes aegypti mosquitoes. Although its effectiveness is well supported by empirical evidence, the underlying molecular mechanisms remain incompletely understood. Current findings indicate that Wolbachia-mediated inhibition of DENV is multifactorial, involving interactions with the endoplasmic reticulum, competition for cellular nutrients, suppression of pro-viral signaling pathways, regulation of host miRNAs, stimulation of mosquito immune responses, and enhancement of viral RNA degradation. These complex and synergistic mechanisms highlight Wolbachia’s potential not only as a tool for vector control but also as a foundation for developing more effective strategies in dengue prevention and management.

Keywords

Wolbachia; Aedes aegypti; Virus replication; Dengue

Full Text:

PDF

References

Tim Riset Kesehatan Dasar 2018 (Indonesia), Indonesia, editors. Laporan nasional Riskesdas 2018. Jakarta: Kementerian Kesehatan, Republik Indonesia, Badan Penelitian dan Pengembangan Kesehatan; 2019.

Muhawarman A. Waspada Penyakit di Musim Hujan. Kementerian Kesehatan Republik Indonesia [Internet]. 2024 [cited 2025 Jul 21]; Available from: https://kemkes.go.id/id/rilis-kesehatan/waspada-penyakit-di-musim-hujan

Mickelson AR, Felton J, Cheschi O, Spacone E, Connors K, Thornsberry J, et al. Infections of Aedes mosquito cells by Wolbachia strains wAu and wMelpop modulate host cellular transcriptomes differently and suppress dengue viral replication. Viruses. 2025;17(7):922.

Edenborough KM, Flores HA, Simmons CP, Fraser JE. Using Wolbachia to eliminate dengue: will the virus fight back? J Virol. 2021;95(13):e0220320.

Utarini A, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Ansari MR, et al. Efficacy of Wolbachia-infected mosquito deployments for the control of dengue. N Engl J Med. 2021;384(23):2177–86.

Ekwudu O, Devine GJ, Aaskov JG, Frentiu FD. Wolbachia strain wAlbB blocks replication of flaviviruses and alphaviruses in mosquito cell culture. Parasit Vectors. 2020;13(1):54.

Loterio RK, Monson EA, Templin R, Bruyne JT, Flores HA, Mackenzie JM, et al. Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and disturb host cell lipid distribution to restrict dengue virus replication bioRxiv. 2023:2023.09.14.557745

Lee WS, Webster JA, Madzokere ET, Stephenson EB, Herrero LJ. Mosquito antiviral defense mechanisms: a delicate balance between innate immunity and persistent viral infection. Parasit Vectors. 2019;12(1):165.

Loterio RK, Monson EA, Templin R, et al. Antiviral Wolbachia strains associate with Aedes aegypti endoplasmic reticulum membranes and induce lipid droplet formation to restrict dengue virus replication. mBio. 2024;15(2):e0249523

Choy MM, Sessions OM, Gubler DJ, Ooi EE. Production of infectious dengue virus in aedes aegypti is dependent on the ubiquitin proteasome pathway. Harris E, editor. PLoS Negl Trop Dis. 2015;9(11):e0004227.

Serrato-Salas J, Hernández-Martínez S, Martínez-Barnetche J, Condé R, Alvarado-Delgado A, Zumaya-Estrada F, et al. De novo DNA synthesis in Aedes aegypti midgut cells as a complementary strategy to limit dengue viral replication. Front Microbiol. 2018;9:801.

Hedges LM, Brownlie JC, O’Neill SL, Johnson KN. Wolbachia and virus protection in insects. Science. 2008;322(5902):702.

Pan X, Zhou G, Wu J, Bian G, Lu P, Raikhel AS, et al. Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti. Proc Natl Acad Sci USA. 2012;109(1):E23–31

Rancès E, Ye YH, Woolfit M, McGraw EA, O’Neill SL. the relative importance of innate immune priming in Wolbachia-mediated dengue interference. PLoS Pathog. 2012;8(2):e1002548.

Zhang G, Hussain M, O’Neill SL, Asgari S. Wolbachia uses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition in Aedes aegypti. Proc Natl Acad Sci USA. 2013;110(25):10276–81.

Koh C, Islam MN, Ye YH, Chotiwan N, Graham B, Belisle JT, et al. Dengue virus dominates lipid metabolism modulations in Wolbachia-coinfected Aedes aegypti. Commun Biol. 2020;3(1):518.

Hussain M, Qi Z, Asgari S. Interaction of the Wolbachia surface protein with a novel pro-viral protein from Aedes aegypti. mBio. 2025;16(1):e0148624.

Bola Olajide O, Olajide JS, Olasehinde O. General perspectives on dengue fever. Clin Microbiol Newsl. 2024;49:1–9.

Flores HA, Taneja De Bruyne J, O’Donnell TB, Tuyet Nhu V, Thi Giang N, Thi Xuan Trang H, et al. Multiple Wolbachia strains provide comparative levels of protection against dengue virus infection in Aedes aegypti. PLoS Pathog. 2020;16(4):e1008433.

Dupuis B, Pocquet N, Failloux AB. Understanding the role of trehalose in interactions between Wolbachia and Aedes aegypti. Front Cell Infect Microbiol. 2025;15:1547873.

Osorio J, Villa-Arias S, Camargo C, Ramírez-Sánchez LF, Barrientos LM, Bedoya C, et al. wMel Wolbachia alters female post-mating behaviors and physiology in the dengue vector mosquito Aedes aegypti. Commun Biol. 2023;6(1):865.

Reyes JIL, Suzuki Y, Carvajal T, Muñoz MNM, Watanabe K. Intracellular interactions between arboviruses and Wolbachia in Aedes aegypti. Front Cell Infect Microbiol. 2021;11:690087.

Mushtaq I, Sarwar MS, Munzoor I. A comprehensive review of Wolbachia-mediated mechanisms to control dengue virus transmission in Aedes aegypti through innate immune pathways. Front Immunol. 2024;15:1434003.

She L, Shi M, Cao T, Yuan H, Wang R, Wang W, et al. Wolbachia mediates crosstalk between miRNA and Toll pathways to enhance resistance to dengue virus in Aedes aegypti. PLoS Pathog. 2024;20(6):e1012296.

Hussain M, Zhang G, Leitner M, Hedges LM, Asgari S. Wolbachia RNase HI contributes to virus blocking in the mosquito Aedes aegypti. iScience. 2023;26(1):105836.

Anders KL, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Andari B, et al. Update to the AWED (Applying Wolbachia to Eliminate Dengue) trial study protocol: a cluster randomised controlled trial in Yogyakarta, Indonesia. Trials. 2020;21(1):429.

Dufault SM, Tanamas SK, Indriani C, Utarini A, Ahmad RA, Jewell NP, et al. Disruption of spatiotemporal clustering in dengue cases by wMel Wolbachia in Yogyakarta, Indonesia. Sci Rep. 2022;12(1):9890.

Ogunlade ST, Adekunle AI, Meehan MT, McBryde ES. Quantifying the impact of Wolbachia releases on dengue infection in Townsville, Australia. Sci Rep. 2023;13(1):14932.

Moretti R, Lim JT, Ferreira AGA, Ponti L, Giovanetti M, Yi CJ, et al. Exploiting Wolbachia as a tool for mosquito-borne disease control: pursuing efficacy, safety, and sustainability. Pathogens. 2025;14(3):285.

DOI: https://doi.org/10.26891/JIK.v20i1.2026.21-29

Refbacks

  • There are currently no refbacks.