It is known that the innate immune response is based on the recognition of viral genomes by cellular receptors. By investigating two of these receptors during infection by dengue and Zika viruses, scientists from the Institut Pasteur discovered that a precise region of the viral genome was recognized by a receptor known as RIG-I. Their discovery paves the way for the future development of vaccines for these diseases.
Cells defend themselves against viral infections by rapidly triggering an innate immune response. This response is activated when RIG-I-like protein receptors (also known as RLRs) recognize viral genomes. Recognition of the genome of a virus initiates a signaling cascade that results in the expression of several hundreds of genes that are capable of blocking various stages of viral replication.
Two of these protein receptors, RIG-I and MDA5, had previously been identified as playing a key role in the innate response against the replication of flaviviruses, a family of mosquito-borne viruses that includes dengue, yellow fever and Zika. However, the exact nature of the viral motifs recognized by RLRs was not known.
Using an RLR-purification technique in conjunction with high-throughput sequencing and bioinformatics analysis, "we demonstrated that a precise region of the genomes of the dengue and Zika viruses (known as the 5' untranslated region) was recognized by RIG-I," explains Nolwenn Jouvenet, a scientist in the Viral Genomics and Vaccination Unit at the Institut Pasteur and last author of the paper. "We also found that MDA5 was not involved in the recognition of these genomes."
Unraveling the molecular mechanisms used by human cells to detect viral infections will help improve understanding of the diseases caused by these viruses. These findings could also pave the way for the development of viral strains that induce a robust innate response and thus could be used as live attenuated vaccines.
There is currently no specific treatment or effective vaccine for dengue or Zika. The only available strategies are to enforce vector mosquito control in endemic areas and take personal protective measures against mosquito bites. These two diseases are transmitted to humans by mosquitoes of the Aedes genus, for which surveillance has been stepped up in France from May to November 2018 since the tiger mosquito (Aedes albopictus) is now present in 42 French départements, twice as many as two years ago.
RIG-I Recognizes the 5’ Region of Dengue and Zika Virus Genomes, Cell Reports, July 10, 2018.
Maxime Chazal1,2,3, Guillaume Beauclair1, Ségolène Gracias1, Valérie Najburg1, Etienne Simon-Lorriere2,3, Frédéric Tangy1, Anastasia Komarova1, Nolwenn Jouvenet1
1. Viral Genomics and Vaccination Unit, Department of Virology, CNRS UMR 3569, Institut Pasteur, Paris, France.
2. Functional Genetics of Infectious Diseases Unit, Institut Pasteur, Paris, France.
3. CNRS UMR2000 Evolutionary Genomics, Modeling and Health, Institut Pasteur, Paris, France.