Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 3:14:1287519.
doi: 10.3389/fmicb.2023.1287519. eCollection 2023.

A tangled threesome: understanding arbovirus infection in Aedes spp. and the effect of the mosquito microbiota

Juan S Mantilla-Granados  1 , Jaime E Castellanos  2 , Myriam Lucía Velandia-Romero  2
Affiliations
Review

A tangled threesome: understanding arbovirus infection in Aedes spp. and the effect of the mosquito microbiota

Juan S Mantilla-Granados et al. Front Microbiol. .

Abstract

Arboviral infections transmitted by Aedes spp. mosquitoes are a major threat to human health, particularly in tropical regions but are expanding to temperate regions. The ability of Aedes aegypti and Aedes albopictus to transmit multiple arboviruses involves a complex relationship between mosquitoes and the virus, with recent discoveries shedding light on it. Furthermore, this relationship is not solely between mosquitoes and arboviruses, but also involves the mosquito microbiome. Here, we aimed to construct a comprehensive review of the latest information about the arbovirus infection process in A. aegypti and A. albopictus, the source of mosquito microbiota, and its interaction with the arbovirus infection process, in terms of its implications for vectorial competence. First, we summarized studies showing a new mechanism for arbovirus infection at the cellular level, recently described innate immunological pathways, and the mechanism of adaptive response in mosquitoes. Second, we addressed the general sources of the Aedes mosquito microbiota (bacteria, fungi, and viruses) during their life cycle, and the geographical reports of the most common microbiota in adults mosquitoes. How the microbiota interacts directly or indirectly with arbovirus transmission, thereby modifying vectorial competence. We highlight the complexity of this tripartite relationship, influenced by intrinsic and extrinsic conditions at different geographical scales, with many gaps to fill and promising directions for developing strategies to control arbovirus transmission and to gain a better understanding of vectorial competence. The interactions between mosquitoes, arboviruses and their associated microbiota are yet to be investigated in depth.

Keywords: Aedes aegypti; Aedes albopictus; RNA interference; Wolbachia; extracellular vesicles; insect specific virus; mosquito-borne disease; vectorial competence.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Infection barriers and immunological mosquito cellular response to arbovirus infection. (A) Immunological signal pathways (I) Toll receptors, (II) IMD, (III) Dome (JAK-STAT), (IV) tyrosine-kinase receptors (RTK), and (V) Notch pathway. (B) Viral entry and RNAi responses produced by mosquitoes cells. (I) small interference RNAs siRNA, (II) Piwi RNAs piRNA, and (III) microRNAs miRNA. Figure produced in BioRender.com.
Figure 2
Figure 2
The interaction of the microbiota with the mosquito immunological response affects arboviral infection. (A) Direct and indirect mechanism of the microorganism could interfere with arbovirus infection, (I) through metabolites (MB) lumen fungus could affect trypsin production, favoring arbovirus survival, (II) change in lectin production, affecting AMPs recognition, and arbovirus entrance (III) production of proteins like p40 facilitating arbovirus recognition by host cells, (IV) MB production that destroy arbovirus envelope, (V) MB that degrade mucin layer, (VI) Immune priming through canonical immunological pathways, increasing AMPs and ROS production, (VII) Wolbachia presence increase oxidative stress, activating Toll pathway, (VIII) Microtubules reorganization induced by Wolbachia presence affecting vesicular traffic, (IX) Wolbachia Rnase production, destroying viral RNA, (X) Wolbachia could also compete with arbovirus for resources like lipids inducing its storage as lipid droplets (LD), (XI) Wolbachia infection can change the interaction between the arbovirus and the insect specific viruses (ISV), (XII) potential effect of Wolbachia infection on the extracellular vesicles infection mechanism used by the arboviruses, (XIII) Changes of microbiota composition by the arbovirus infections, associated to the immunological response activation and AMPs production. (B) Interactions of previous viral infections with new arboviral infection, (I), immune priming mediated by interference RNA (iRNAs), (II) Endogenization of non-retroviral elements (NIRVS) from viral RNA and ISV RNA, through the insect autonomous transposable elements (TEs) and its retrotranscriptase (RT), creating viral intermediaries DNA (VDNA) for i RNA production, (III) Overexpression of proviral proteins for ISV infection, (IV) Synthesis of non-functional viral proteins, promoting non-functional viral particles, (V) subgenomic flaviviral RNAs (sfRNA) interfere with iRNAs responses, (VI) arbovirus infection can also change ISV presence (mostly enhance), probably by the changes on mosquito immunological response like interfering with iRNA response.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Abduljalil J. M., Abd Al Galil F. M. (2022). Molecular pathogenesis of dengue virus infection in Aedes mosquitoes. J. Insect Physiol. 138, 104367. 10.1016/j.jinsphys.2022.104367 - DOI - PubMed
    1. Ahmad N. A., Mancini M. V., Ant T. H., Martinez J., Kamarul G. M. R., Nazni W. A., et al. . (2021). Wolbachia strain wAlbB maintains high density and dengue inhibition following introduction into a field population of Aedes aegypti. Philos. Trans. R. Soc. London. Ser. B, Biol. Sci. 376, 20190809. 10.1098/rstb.2019.0809 - DOI - PMC - PubMed
    1. Ahmad N. A., Vythilingam I., Lim Y. A. L., Zabari N. Z. A. M., Lee H. L. (2017). Detection of Wolbachia in Aedes albopictus and their effects on chikungunya virus. Am. J. Trop. Med. Hyg. 96, 148–156. 10.4269/ajtmh.16-0516 - DOI - PMC - PubMed
    1. Ajamma Y. U., Onchuru T. O., Ouso D. O., Omondi D., Masiga D. K., Villinger J. (2018). Vertical transmission of naturally occurring Bunyamwera and insect-specific flavivirus infections in mosquitoes from islands and mainland shores of Lakes Victoria and Baringo in Kenya. PLoS Negl. Trop. Dis. 12, e0006949. 10.1371/journal.pntd.0006949 - DOI - PMC - PubMed
    1. Alencar J., de Mello C. F., Marcondes C. B., Guimarães A. É., Toma H. K., Bastos A. Q., et al. . (2021). Natural infection and vertical transmission of Zika virus in sylvatic mosquitoes Aedes albopictus and Haemagogus leucocelaenus from Rio de Janeiro, Brazil. Trop. Med. Infect. Dis. 6, 99. 10.3390/TROPICALMED6020099 - DOI - PMC - PubMed

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project was funded by Minciencias and Universidad El Bosque, contract 891-2019. The funding sources had no role in information review or preparation of the manuscript.