More Than a Gut Feeling About Mosquito-Borne Viruses

Deciphering the immune response in mosquitoes to the O’nyong nyong virus may lead to new broad-spectrum antiviral targets.

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Notorious for their ability to transmit diseases such as malaria and dengue hemorrhagic fever, mosquitoes are a threat to global health. Curiously, the Anopheles mosquito is a potent vector for the malaria parasite but is known to be less effective than the Aedes and Culex mosquitoes at transmitting viruses. In fact, the Anopheles mosquito is known to transmit just one virus—the O’nyong nyong virus (ONNV), which belongs to a family of alphaviruses that include the Chikungunya virus.

Seeking to understand how ONNV manages to circumvent the Anopheles mosquito’s immune system where other viruses have failed, scientists led by Guillaume Carissimo at A*STAR’s Singapore Immunology Network (SIgN) studied the expression of immune-related genes in ONNV-infected mosquitoes. The research was done in collaboration with the Pasteur Institute in France.

The researchers first determined that the ideal moment to collect mRNA from the mosquitos was three days after the insects had been fed a bloodmeal containing ONNV. At this time point, the ‘battle’ between ONNV and the mosquito’s immune system is taking place in the mosquito’s midgut, which allows the team to assess which genes are expressed differently during this critical phase of first contact.

“Our earlier findings showed that the immune pathways in mosquitoes are compartmentalized, which means that it is important to study the immune response in the midgut before systemic infection takes place,” said Carissimo.

The team found that a “surprisingly narrow” range of genes was differentially regulated upon ONNV infection of the mosquito midgut—they observed changes in the expression of only 30 mRNA transcripts and just one microRNA transcript between uninfected and ONNV-infected mosquitoes. Digging deeper, the researchers identified that two key regulators of the mosquito’s innate immune response—the transcription factors STAT and Rel2—were responsible for altering the expression of vast and distinct clusters of mRNA and microRNA genes.

These findings could pave the way for novel methods of mosquito control, Carissimo noted. “There are very intriguing and interesting possibilities that could be harnessed and modified to recognize and neutralize pathogens in modified vectors,” he said.

Carissimo’s team plans to continue studying mosquito-virus and human-virus interactions, with a special emphasis on the Chikungunya virus and ONNV. “Implementing systems and technologies to study the conserved and specialized virus-hosts interactions will yield attractive targets for broad-spectrum antiviral targets, as well as fundamental knowledge on how viruses can modulate immune responses in humans,” he said.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN).