Abstract
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 apoptosis 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 arbovirus transmission.
Highlights
In recent decades, dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses have emerged as global public health issues, with over 50% of the world population at risk for infection [1]
Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses are responsible for large number of death and debilitation around the world
SGs were collected at 14 days post oral infection with dengue virus serotype 2 PVP110 (DENV2) and Zika virus Paraiba_01/2015 (ZIKV), and at seven dpi with chikungunya virus SGP011 (CHIKV) to account for variability between virus extrinsic incubation periods (EIP) [29,30]
Summary
Dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses have emerged as global public health issues, with over 50% of the world population at risk for infection [1]. DENV infects an estimated 390 million people yearly, causing a wide range of clinical manifestations from mild fever to shock syndrome and fatal hemorrhage [2]. ZIKV recently emerged as an epidemic virus, infecting 1.5 million people over the past five years [3]. CHIKV emerged as an epidemic virus in 2004, and has infected more than 6 million people [5]. It causes mild fever but can result in musculoskeletal inflammation, leading to long-term polyarthralgia. Climate change and global travel, arboviral outbreaks are unlikely to recede in the near future [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
