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.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301069 | PMC |
http://dx.doi.org/10.1016/j.isci.2024.110391 | DOI Listing |
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