GW4869 inhibitor affects vector competence and tick-borne flavivirus acquisition and transmission by blocking exosome secretion.

iScience

Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville TN 37996, USA.

Published: August 2024

Exosomes/extracellular vesicles (EVs) are essential for the successful transmission of flaviviruses from vector to vertebrate host. Arthropod-EVs are envisioned as important target for blocking the transmission of vector-borne viral diseases. In this study, we show that the selective inhibition of EVs secretion by sphingomyelinase inhibitor, GW4869 significantly reduces vector efficiency and competence in acquiring and transmitting tick-borne flaviviruses. We show that GW4869 reduces EVs release from Langat Virus (LGTV)-infected adult tick salivary glands (SGs). GW4869 treatment showed reduced dissemination of LGTV in SGs and other tissues within ticks. Decreased release of SG-EVs directly correlated with reduced tick blood-feeding efficiency, engorgement weights, and reduction in LGTV acquisition/transmission. Our data indicates that LGTV infection significantly improves molting/fitness, and survival efficiency of ticks and GW4869 alone affects the repletion rates of blood-feeding naïve-ticks. Overall, we provide evidence for GW4869 potential use as therapeutic agent in the tick control and prevention of tick-borne flaviviral transmission.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301069PMC
http://dx.doi.org/10.1016/j.isci.2024.110391DOI Listing

Publication Analysis

Top Keywords

gw4869 reduces
8
gw4869
6
gw4869 inhibitor
4
inhibitor vector
4
vector competence
4
competence tick-borne
4
tick-borne flavivirus
4
flavivirus acquisition
4
transmission
4
acquisition transmission
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!