Biased virus transmission following sequential coinfection of Aedes aegypti with dengue and Zika viruses

• Published in: PLoS neglected tropical diseases Vol. 18; no. 4; p. e0012053
• Main Authors: Peng, Jiameng, Zhang, Meichun, Wang, Gang, Zhang, Dongjing, Zheng, Xiaoying, Li, Yongjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2024; Public Library of Science (PLoS)
• Subjects: Aedes; Aedes aegypti; Animals; Aquatic insects; Arboviruses; Biology and life sciences; Chikungunya virus; Climate change; Coinfection - epidemiology; Culicidae; Dengue; Dengue - epidemiology; Dengue fever; Dengue Virus; Distribution; Evaluation; Human diseases; Innate immunity; International trade; Lipid metabolism; Lipids; Medicine and Health Sciences; Metabolism; Mosquito Vectors; Mosquitoes; Pandemics; Public health administration; Replication; RNA-mediated interference; Urbanization; Vector-borne diseases; Virus-vector relationships; Viruses; Zika Virus; Zika Virus Infection; China
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0012053

Mosquito-borne arboviruses are expanding their territory and elevating their infection prevalence due to the rapid climate change, urbanization, and increased international travel and global trade. Various significant arboviruses, including the dengue virus, Zika virus, Chikungunya virus, and yellow fever virus, are all reliant on the same primary vector, Aedes aegypti. Consequently, the occurrence of arbovirus coinfection in mosquitoes is anticipated. Arbovirus coinfection in mosquitoes has two patterns: simultaneous and sequential. Numerous studies have demonstrated that simultaneous coinfection of arboviruses in mosquitoes is unlikely to exert mutual developmental influence on these viruses. However, the viruses' interplay within a mosquito after the sequential coinfection seems intricated and not well understood. We conducted experiments aimed at examining the phenomenon of arbovirus sequential coinfection in both mosquito cell line (C6/36) and A. aegypti, specifically focusing on dengue virus (DENV, serotype 2) and Zika virus (ZIKV). We firstly observed that DENV and ZIKV can sequentially infect mosquito C6/36 cell line, but the replication level of the subsequently infected ZIKV was significantly suppressed. Similarly, A. aegypti mosquitoes can be sequentially coinfected by these two arboviruses, regardless of the order of virus exposure. However, the replication, dissemination, and the transmission potential of the secondary virus were significantly inhibited. We preliminarily explored the underlying mechanisms, revealing that arbovirus-infected mosquitoes exhibited activated innate immunity, disrupted lipid metabolism, and enhanced RNAi pathway, leading to reduced susceptibility to the secondary arbovirus infections. Our findings suggest that, in contrast to simultaneous arbovirus coinfection in mosquitoes that can promote the transmission and co-circulation of these viruses, sequential coinfection appears to have limited influence on arbovirus transmission dynamics. However, it is important to note that more experimental investigations are needed to refine and expand upon this conclusion.