Study in PNAS found that mosquitoes cut the virus genome into virus-derived short-interfering RNAs.

Though it has been long thought that mosquitoes are oblivious to the viruses they transmit, Virginia Tech researchers have shown that they actively fight against the infection by cutting strands of code at the cellular level.

Virus-derived short-interfering RNAs (viRNAs), generated by the mosquito’s immune response to infection, balance the interactions between the mosquito and virus. “If the mosquito is not able to cut up the virus genome into viRNAs, an otherwise invisible infection becomes fatal for both the mosquito and the virus,” explains Kevin M. Myles, Ph.D., assistant professor of entomology at Virginia Tech. “In other words, to complete the circle and be transmitted back to a vertebrate host, the virus must submit, to some extent, to the mosquito’s antiviral response.”

The researchers started with the arthropod-borne virus Sindbis, a model virus for a wide variety of mosquito-transmitted viruses that cause diseases in humans. Next, they infected an Aedes aegypti, a mosquito that is an important vector of yellow fever and dengue.

In response, the mosquito immune system generated viRNAs, which make up 10% or more of total cellular small RNAs. Finally, the team altered the Sindbis genome so that it would carry a protein known to suppress the ability of a cell to cut up virus genomes into viRNAs.

The study points to the potential of therapeutic approaches using knowledge gained from studying viRNAs from infected mosquitoes to control the pathogenesis of these viruses in mammalian hosts. Additional research will be required to determine how to manipulate the mosquito’s immune response.

The results appear in the online early edition of Proceedings of the National Academy of Sciences for the week of December 1–5.

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