Tinkering with extracellular vesicles viruses evolve new infectious units

Diosa-Toro, Mayra; Strilets, Tania; Yeh, Shu-Lan; García-Blanco, Mariano A.

doi:10.21037/exrna-21-26

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“…While it is formally possible that sfRNA is packaged in DENV2 virions in the saliva, as proposed in a recent report studying human EVs [ 17 ], we do not favor this conclusion based on the differential DMSO sensitivity observed for gRNA and sfRNA and our previous data [ 8 ]. EVs are well known vehicles of coding and noncoding RNAs, including viral RNAs [ 29 – 31 ]. Our observations of EVs in mosquito saliva labelled for DENV2 3’UTR and gRNA, is consistent with previous studies using DENV and other Flaviviridae [ 21 , 32 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity

et al. 2023

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Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3’UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3’UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission.

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