Current Insights into Superinfection Exclusion in Insect-Specific Orthoflaviviruses

The Orthoflavivirus genus includes a variety of human-pathogenic, mosquito-borne flaviviruses (MBFs) including dengue, Zika, and West Nile viruses, which pose significant global public health threats. Insect-specific flaviviruses (ISFs) are another group within the genus that exclusively replicate in mosquitoes and are incapable of infecting vertebrates. ISFs have recently attracted growing research interest due to their potential applications in vaccine development. In addition, multiple studies have demonstrated that prior infection with ISFs such as Palm Creek virus and Binjari virus can suppress subsequent infection with human-pathogenic MBFs. This phenomenon, known as superinfection exclusion (SIE), opens the avenue for the potential applications of ISFs in MBF transmission control. This prompted a growing number of studies into ISFs and their interactions with MBFs in mosquito hosts. In this review, we provide an overview on ISFs, with a particular emphasis on the capacity of different ISFs to cause SIE, the current insights into the mechanisms of this phenomenon, and the potential use of ISFs in the SIE-based biocontrol strategies.