Sphingomyelins in mosquito saliva modify the host lipidome to enhance transmission of flaviviruses by promoting viral protein levels
Medkour, H.; Pruvost, L.; Gong, X.; Vaissayre, V.; Boutinaud, P.; Revel, J.; Hitakarun, A.; Sornjai, W.; Zoladek, J.; Smith, D. R.; Nisole, S.; Nolte-t Hoen, E.; bertrand-Michel, J.; Misse, D.; Marti, G.; Pompon, J.
Show abstract
Mosquito saliva plays a determining role in flavivirus transmission. Here, we discover and elucidate how salivary lipids enhance transmission. Building upon our discovery of salivary extracellular vesicles (EV), we determined that lipids within mosquito EVs, and neither within human EVs nor virions, enhance infection for flaviviruses in primary cell types relevant for transmission. Mechanistically, mosquito EV-lipids specifically promote viral protein levels by reducing ER-associated degradation. Infection enhancement is caused by sphingomyelins within mosquito salivary EVs that elevate sphingomyelin concentration within host cells. Transmission assays showed that mosquito EV-lipids exacerbate disease severity. Our study reveals that EV-associated sphingomyelins within mosquito saliva enhance transmission for multiple flaviviruses by reconfiguring the host lipidome to promote viral protein levels and the resulting skin infection. Our findings open a new dimension centered on lipids in the interplay between hosts, mosquitoes and flaviviruses that determine transmission, unveiling lipids as a new pan-flavivirus target. HighlightsO_LILipids within mosquito extracellular vesicles (EVs) enhance infection in primary skin and immune cells for multiple flaviviruses. C_LIO_LIMosquito EV-lipids increase flaviviral protein levels by dampening ER-associated degradation. C_LIO_LISphingomyelins within salivary EVs are responsible for the infection enhancement by altering host lipidome. C_LIO_LICo-injection of mosquito EV-lipids exacerbate disease severity. C_LI
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A global lipid map defines a network essential for Zika virus replication 97%
- An intranasal nanoparticle STING agonist has broad protective immunity against respiratory viruses and variants 96%
- The encephalomyocarditis virus Leader promotes the release of virions inside extracellular vesicles via the induction of secretory autophagy 95%
Similar papers in this journal
- Human brain cell types shape host-rabies virus transcriptional interactions revealing a preexisting pro-viral astrocyte subpopulation 94%
- Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant 94%
- Systems immunology of transcriptional responses to viral infection identifies conserved antiviral pathways across macaques and humans 93%
Similar papers in this journal
- Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS 95%
- Single B cell transcriptomics identifies multiple isotypes of broadly neutralizing antibodies against flaviviruses 95%
- Antigen flexibility supports the avidity of hemagglutinin-specific antibodies at low antigen densities 94%
Similar papers in this journal
- A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing 94%
- Asymmetric HIV-1 envelope trimers bound to one and two CD4 molecules are intermediates during membrane binding 94%
- Impact of circulating SARS-CoV-2 variants on mRNA vaccine-induced immunity in uninfected and previously infected individuals 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.