Prior Eilat virus infection delayed dissemination of Chikungunya virus in the yellow fever mosquito (Aedes aegypti)
Alphaviruses are transmitted by mosquitoes and infect many animals including birds, horses, human and non-human primates. The resulting infection can cause disease ranging from severe arthritis to fatal encephalitis. The ability to infect mosquitoes and animals ensures the viruses can persist in nature via the mosquito/animal cycle, serving as a reservoir for potential future epidemics. Currently, there are no licensed therapeutics or vaccines to treat and/or prevent alphavirus infection. However, any strategy that disrupts the mosquito/animal cycle of pathogenic viruses could potentially reduce or prevent transmission. We recently discovered a unique alphavirus, named Eilat virus (EILV), that is a close relative of pathogenic alphaviruses, however, unlike other viruses, it is unable to enter and replicate in mammalian cells but readily infects mosquito cells. We utilized EILV to investigate whether an established EILV infection can reduce or prevent subsequent infection with a pathogenic alphavirus. Our results demonstrate that prior EILV infection of mosquito cells and mosquitoes can reduce and delay replication of subsequent pathogenic alphavirus infection.
The idea for the study came from experiments first conducted by McKinney in the 1920s in plants, where a viral infection prevents or reduces subsequent infection with a closely related virus. This phenomenon is termed superinfection exclusion or homologous/heterologous interference, and was subsequently developed as a tool to reduce pathogenic infection in plants. Soon after its discovery, homologous and heterologous interference was shown with alphaviruses in model mosquito and mammalian cell lines. However, since all mosquito-borne alphaviruses can infect mosquitoes and animals as well as cause severe disease, it renders them undesirable for any potential application to reduce or prevent alphavirus transmission. In contrast, the inability of EILV to infect mammalian cells makes the virus suitable to investigate the superinfection exclusion phenomenon.
The results from initial experiments performed with recombinant viruses expressing green or red fluorescent proteins showed dramatic reduction in replication of pathogenic alphaviruses in a model Aedes albopictus cell line. These promising results led us to investigate the potential of EILV to induce the similar phenomenon in mosquitoes. However, EILV is unable to establish infection via oral infection, a route typical for virus infection. We injected mosquitoes with EILV to establish an infection, however EILV replication was lower than that shown for other alphaviruses. Nevertheless, we super-infected those mosquitoes with chikungunya virus (CHIKV), and surprisingly, even with lower levels of EILV infection, the interference induced by EILV was enough to slow the spread of CHIKV in mosquitoes. Our results show that EILV, and likely similar viruses in other arbovirus families, can be potentially developed to reduce or prevent transmission of pathogenic viruses.
Introducing the author