Multiple orthoflaviviruses secrete sfRNA in mosquito saliva to promote transmission by inhibiting MDA5-mediated early interferon response
Abstract
Numerous orthoflaviviruses transmitted through the bites of different mosquito species infect more than 500 million people annually. Skin infection at the bite site represents a critical and conserved step in transmission and a deeper understanding of this process will promote the design of broad-spectrum interventions. Here, we identify and characterize a transmission-enhancing viral factor in mosquito saliva that is shared across orthoflaviviruses. Saliva from West Nile virus-infected Culex and Zika virus-infected Aedes contains a viral non-coding RNA, subgenomic flaviviral RNA (sfRNA), within lipid vesicles distinct from virions. Higher concentration of sfRNA in infectious saliva positively correlates with infection intensity in human cells and skin explants. Early sfRNA delivery into transmission-relevant skin cell types and human skin explant demonstrate that sfRNA is responsible for the infection enhancement. Co-inoculation of sfRNA in a mouse model of transmission enhanced skin infection and worsened disease severity, supporting the role of salivary sfRNA as a transmission-enhancer. Mechanistically, salivary sfRNA attenuates early interferon response in human skin cells and skin explants by disrupting MDA5 signaling. Our results, derived from two distinct orthoflaviviruses and supported by prior studies, establish salivary sfRNA as a pan-orthoflavivirus transmission-enhancing factor driven by a conserved viral non-coding RNA.
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BibTeX
@article{serratopomar2026multiple,
title = {{Multiple orthoflaviviruses secrete sfRNA in mosquito saliva to promote transmission by inhibiting MDA5-mediated early interferon response}},
author = {Idalba Serrato-Pomar and Hacène Medkour and Louise Belleville and Kachaporn Jintana and Lauryne Pruvost and Norman Schneider and Mihra Tavadia and Jim Zoladek and Florian Rachenne and Zoé Roux and Quentin Narpon and Felix Rey-Cadilhac and Soléna Rossi and Stephanie French and Cassandra Modahl and Carole Ginibre and Bethsabée Scheid and Wannapa Sornjai and Elliott F Miot and Duncan R Smith and Rodolphe Hamel and Oleg Medianikov and Dorothée Missé and Sébastien Nisole and Julien Pompon},
journal = {Nature Communications},
year = {2026},
month = aug,
doi = {10.1038/s41467-026-77288-4},
url = {https://hal.science/hal-05784152v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multiple orthoflaviviruses secrete sfRNA in mosquito saliva to promote transmission by inhibiting MDA5-mediated early interferon response
AU - Idalba Serrato-Pomar
AU - Hacène Medkour
AU - Louise Belleville
AU - Kachaporn Jintana
AU - Lauryne Pruvost
AU - Norman Schneider
AU - Mihra Tavadia
AU - Jim Zoladek
AU - Florian Rachenne
AU - Zoé Roux
AU - Quentin Narpon
AU - Felix Rey-Cadilhac
AU - Soléna Rossi
AU - Stephanie French
AU - Cassandra Modahl
AU - Carole Ginibre
AU - Bethsabée Scheid
AU - Wannapa Sornjai
AU - Elliott F Miot
AU - Duncan R Smith
AU - Rodolphe Hamel
AU - Oleg Medianikov
AU - Dorothée Missé
AU - Sébastien Nisole
AU - Julien Pompon
PY - 2026
DA - 2026/08/29
JO - Nature Communications
DO - 10.1038/s41467-026-77288-4
UR - https://hal.science/hal-05784152v1
AB - Numerous orthoflaviviruses transmitted through the bites of different mosquito species infect more than 500 million people annually. Skin infection at the bite site represents a critical and conserved step in transmission and a deeper understanding of this process will promote the design of broad-spectrum interventions. Here, we identify and characterize a transmission-enhancing viral factor in mosquito saliva that is shared across orthoflaviviruses. Saliva from West Nile virus-infected Culex and Zika virus-infected Aedes contains a viral non-coding RNA, subgenomic flaviviral RNA (sfRNA), within lipid vesicles distinct from virions. Higher concentration of sfRNA in infectious saliva positively correlates with infection intensity in human cells and skin explants. Early sfRNA delivery into transmission-relevant skin cell types and human skin explant demonstrate that sfRNA is responsible for the infection enhancement. Co-inoculation of sfRNA in a mouse model of transmission enhanced skin infection and worsened disease severity, supporting the role of salivary sfRNA as a transmission-enhancer. Mechanistically, salivary sfRNA attenuates early interferon response in human skin cells and skin explants by disrupting MDA5 signaling. Our results, derived from two distinct orthoflaviviruses and supported by prior studies, establish salivary sfRNA as a pan-orthoflavivirus transmission-enhancing factor driven by a conserved viral non-coding RNA.
SN - 2041-1723
SN - 2041-1723
ER -