Mosquitoes are well known for spreading viruses such as dengue virus and Japanese encephalitis virus. However, not all mosquito species can transmit every virus. For example, Aedes aegypti mosquitoes are efficient carriers of dengue virus, while other species, such as Culex quinquefasciatus, are not. Scientists have long wondered why certain mosquito species are compatible with specific flaviviruses while others are not.
Researchers from Tsinghua University have uncovered an important mechanism that helps explain this selectivity. They found that once flaviviruses enter the mosquito body cavity, called the haemocoel, free virus particles are quickly inactivated by the acidic environment of the mosquito haemolymph, which is the insect equivalent of blood. This means the virus cannot rely on traditional free-floating viral particles to spread from cell to cell.
Instead, the virus uses extracellular vesicles to move through the mosquito. Extracellular vesicles, sometimes referred to as exosomes, are small membrane-bound particles released by cells. In this case, the vesicles carry replication-competent viral nucleocapsids, which contain the genetic material of the virus. These vesicles protect the virus from the acidic haemolymph and allow it to infect new cells.
A key protein in mosquitoes, called valosin-containing protein, or VCP, plays a central role in this process. The researchers discovered that VCP binds to the viral capsid protein. This interaction allows viral nucleocapsids to be packaged into extracellular vesicles. Importantly, the viral capsid from dengue virus selectively binds to the VCP of its natural vector, Aedes aegypti, but not to the VCP of Culex quinquefasciatus, which is normally an incompetent vector for dengue.
The team went further to test this specificity. When they replaced the dengue virus capsid with that of Japanese encephalitis virus, the modified virus was able to survive and spread in Culex mosquitoes, which are natural vectors for Japanese encephalitis virus. They also identified two specific amino acids in VCP that determine binding specificity. By modifying these amino acids in Culex VCP, they made Culex mosquitoes susceptible to dengue virus after direct injection.
These findings provide a molecular explanation for why certain mosquito species can transmit specific flaviviruses. By showing that extracellular vesicles are the primary vehicles for viral spread within mosquitoes, and that species-specific protein interactions control this process, the research sheds light on the compatibility between virus and vector. Understanding these mechanisms may ultimately help guide new strategies to interrupt mosquito-borne disease transmission.
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