Identification of Mosquito-Specific Viruses and Their Role in Virus-Virus-Host Interactions

Abstract

The ”virosphere” refers to the entire realm of viruses that exist on Earth. It includes all types of viruses, but up until recently, research has been mainly focused on those that directly affect humans and other animal or plant species of economic relevance.Yet, the virosphere is estimated to be incredibly vast, with millions of different viral species, and it is believed that many more viruses are yet to be discovered. The study of the virosphere is crucial for understanding the diversity, evolution, and ecology of viruses and their interactions with their hosts. It is also important for identifying potential threats to human and animal health, such as emerging infectious diseases, and for developing strategies to prevent and control viral infections. One part of the virosphere are arboviruses, or arthropod-borne viruses, a group of viruses that are transmitted by arthropods such as mosquitoes, ticks, and sandflies. Arboviral diseases, including dengue fever, chikungunya, Zika fever, West Nile fever, and yellow fever, have a significant impact on global public health. The emergence and re-emergence of arboviral diseases have become a major concern worldwide due to their increasing incidence and geographic spread. While discovery and description of arboviruses primarily emanated from ’classical’ virological research, the discovery of new virus species, and even whole families, is now often due to the proliferation of advanced sequencing technologies and bioinformatics tools. Another part of the virosphere, that is of some relevance to arboviruses, are insect- or mosquito-specific viruses. These are a group of viruses that have co-evolved with their insect hosts, particularly mosquitoes, and do not infect vertebrates. These viruses have recently received increasing attention due to their potential as a tool for controlling mosquito-borne diseases. Research on insect- or mosquitospecific viruses is essential to understand their biology, evolution, and ecology as well as characterizing their potential to reduce the transmission of mosquito-borne diseases. The presented study is a combined approach, using both sequencing and bioinformatical analysis as well as ’classical’ virological and molecular techniques, to investigate the relationships of mosquito-specific viruses, arboviruses and the mosquito immune-system. Next-generation sequencing techniques were used to identify viral species from field samples. Small RNA sequencing was used to further analyse the interactions of the discovered viruses with the mosquito antiviral RNA interference machinery. Further, experiments were performed to analyse the influence of key effector proteins, Dicer and Argonaute, on the replication of these viruses. Finally, experiments on the interactions of mosquito-specific viruses with arboviruses, focused on viral replication and regulation of the host RNA interference system, were performed. In conclusion, the aggregated data expands our knowledge on the complex virus-virus-host interactions and supplements further approaches in studying mosquito-specific viruses as tools for arbovirus transmission control.