Aedes aegypti and Ae. albopictus microbiome/virome: new strategies for controlling arboviral transmission?

Abstract

Aedes aegypti and Aedes albopictus are the main vectors of highly pathogenic viruses for humans, such as dengue (DENV), chikungunya (CHIKV), and Zika (ZIKV), which cause febrile, hemorrhagic, and neurological diseases and remain a major threat to global public health. The high ecological plasticity, opportunistic feeding patterns, and versatility in the use of urban and natural breeding sites of these vectors have favored their dispersal and adaptation in tropical, subtropical, and even temperate zones. Due to the lack of available treatments and vaccines, mosquito population control is the most effective way to prevent arboviral diseases. Resident microorganisms play a crucial role in host fitness by preventing or enhancing its vectorial ability to transmit viral pathogens. High-throughput sequencing and metagenomic analyses have advanced our understanding of the composition and functionality of the microbiota of Aedes spp. Interestingly, shotgun metagenomics studies have established that mosquito vectors harbor a highly conserved virome composed of insect-specific viruses (ISV). Although ISVs are not infectious to vertebrates, they can alter different phases of the arboviral cycle, interfering with transmission to the human host. Therefore, this review focuses on the description of Ae. aegypti and Ae. albopictus as vectors susceptible to infection by viral pathogens, highlighting the role of the microbiota-virome in vectorial competence and its potential in control strategies for new emerging and re-emerging arboviruses.

Keywords: Arbovirus; ISV; Metagenomics; Microbiota; Vectors; Virome.

Fig. 1

The urban cycle of arboviruses in humans and mosquitoes. Figure created with BioRender.com

Fig. 2

Aedes mosquito–microbiota–arbovirus interactions may modulate vectorial competence. Some viral regulatory strategies include the following: Modulation of physical barriers in midgut epithelial cells (MEC). Serratia marcescens by releasing Sm enhancin protein and the fungus Talaromyces by suppressing the expression of digestive enzymes (trypsin) in the midgut of Aedes can promote susceptibility to DENV infection. Activation of immune response signaling pathways and release of antipathogenic components. Wolbachia in the presence of arboviruses can induce antimicrobial peptides (AMP), melanization, and the production of reactive oxygen species (ROS), among others, that restrict arboviral activity. Release of antipathogenic compounds. Chromobacterium sp. Panama (Csp_P), by degrading the arbovirus coat protein, limits the replication of DENV and ZIKV, while Serratia odorifera participates in the interaction between P40 polypeptide and prohibitin, proteins associated with DENV and CHIKV infection in Aedes. Red boxes indicate interactions that increase vector competence (susceptibility to virus infection). Blue boxes indicate interactions that decrease vector competence (resistance to virus infection). CHIKV chikungunya virus, ZIKV Zika virus, DENV dengue virus, ROS reactive oxygen species, AMP antimicrobial peptides, miRNA microRNA, MEC midgut epithelial cells, P40 polyvinentide P40, Pr prohibitin. Figure created with BioRender.com

Fig. 3

Schematic summary of some characteristics of the Aedes mosquito virome from metagenomic studies. The Aedes virome is formed by arboviruses and in greater proportion by insect-specific viruses (ISV). Arboviruses are pathogenic viruses that are transmitted to humans by mosquito vectors (dual host), while ISVs are viruses that replicate exclusively in insects and are not capable of infecting humans (single host). ISVs possibly evolved and diversified with their insect hosts. Some ISV species could potentially modulate vector competence in Aedes spp. Advances in vector viromics may contribute to the development of strategies to control and prevent arboviral diseases. Figure created with BioRender.com

Fig. 4

Conservation of insect-specific viruses (ISV) (virome) in Ae. aegypti and Ae. albopictus in countries of different geographical areas of the world. Pink circles indicate the presence of shared ISVs in Ae. aegypti and Ae. albopictus, yellow circles indicate unique ISVs in Ae. aegypti, and blue circles indicate unique ISVs in Ae. albopictus. Aust Australia, Barb Barbados, Bra Brazil, Nig Nigeria, Guad Guadeloupe, Ken Kenya, PR Puerto Rico, Suiz Switzerland, Tha Thailand, USA United States of America