JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands

Avisha Chowdhury (1) , Cassandra M. Modahl (1) , Siok Thing Tan (1) , Benjamin Wong Wei Xiang (2) , Dorothée Missé (3) , Thomas Vial (2) , R. Manjunatha Kini (1) , Julien Pompon (2, 4)

1 NUS - National University of Singapore
2 Duke-NUS Medical School [Singapore]
3 MIVEGEC-iHAT - Interhuman Arbovirus Transmission
4 MIVEGEC - Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle

Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However , there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N-terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apopto-sis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbo-virus transmission.

Domaines: Immunité innée; Immunité adaptative; Médecine vétérinaire et santé animale

Avisha Chowdhury, Cassandra M. Modahl, Siok Thing Tan, Benjamin Wong Wei Xiang, Dorothée Missé, et al.. JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands. PLoS Pathogens, 2020, 16 (8), pp.e1008754. ⟨10.1371/journal.ppat.1008754⟩. ⟨hal-02958937⟩