Sand fly saliva reprograms skin fibroblasts to enhance arbovirus infection

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F25%3A10505486" target="_blank" >RIV/00216208:11310/25:10505486 - isvavai.cz</a>

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oTfJbeFm7b" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=oTfJbeFm7b</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.isci.2025.113854" target="_blank" >10.1016/j.isci.2025.113854</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Sand fly saliva reprograms skin fibroblasts to enhance arbovirus infection

Popis výsledku v původním jazyce

Arbovirus transmission by sand flies is a growing public health concern, yet the early skin events shaping infection outcomes remain undefined. We establish a mouse model of Toscana virus (TOSV) infection that incorporates sand fly salivary factors to mimic natural transmission. Saliva from two distinct sand fly genera significantly enhanced infection and promoted neurological signs and joint inflammation, recapitulating key features of human TOSV disease. In the skin, dermal macrophages and fibroblasts were the main infected cell types, but only fibroblasts generated infectious virus. Saliva reprogrammed fibroblasts into a wound-healing state permissive to viral replication, driving local viral amplification, systemic spread, and thereby clinical disease. These findings identify skin fibroblasts as central determinants of host susceptibility and reveal that sand fly saliva actively remodels the skin to exacerbate viral pathogenesis. This work redefines the skin&apos;s role in sand fly-transmitted infection and highlights new targets for therapeutic and vaccine development.

Název v anglickém jazyce

Sand fly saliva reprograms skin fibroblasts to enhance arbovirus infection

Popis výsledku anglicky

Arbovirus transmission by sand flies is a growing public health concern, yet the early skin events shaping infection outcomes remain undefined. We establish a mouse model of Toscana virus (TOSV) infection that incorporates sand fly salivary factors to mimic natural transmission. Saliva from two distinct sand fly genera significantly enhanced infection and promoted neurological signs and joint inflammation, recapitulating key features of human TOSV disease. In the skin, dermal macrophages and fibroblasts were the main infected cell types, but only fibroblasts generated infectious virus. Saliva reprogrammed fibroblasts into a wound-healing state permissive to viral replication, driving local viral amplification, systemic spread, and thereby clinical disease. These findings identify skin fibroblasts as central determinants of host susceptibility and reveal that sand fly saliva actively remodels the skin to exacerbate viral pathogenesis. This work redefines the skin&apos;s role in sand fly-transmitted infection and highlights new targets for therapeutic and vaccine development.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/LX22NPO5103" target="_blank" >LX22NPO5103: Národní institut virologie a bakteriologie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

iScience

ISSN

2589-0042

e-ISSN

2589-0042

Svazek periodika

28

Číslo periodika v rámci svazku

11

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

22

Strana od-do

113854

Kód UT WoS článku

001614873200013

EID výsledku v databázi Scopus

2-s2.0-105020780729