Immature particles and capsid-free viral RNA produced by Yellow fever virus-infected cells stimulate plasmacytoid dendritic cells to secrete interferons

Scientific Reports
Laura SinigagliaNolwenn Jouvenet

Abstract

Plasmacytoid dendritic cells (pDCs) are specialized in the production of interferons (IFNs) in response to viral infections. The Flaviviridae family comprises enveloped RNA viruses such as Hepatitis C virus (HCV) and Dengue virus (DENV). Cell-free flaviviridae virions poorly stimulate pDCs to produce IFN. By contrast, cells infected with HCV and DENV potently stimulate pDCs via short-range delivery of viral RNAs, which are either packaged within immature virions or secreted exosomes. We report that cells infected with Yellow fever virus (YFV), the prototypical flavivirus, stimulated pDCs to produce IFNs in a TLR7- and cell contact- dependent manner. Such stimulation was unaffected by the presence of YFV neutralizing antibodies. As reported for DENV, cells producing immature YFV particles were more potent at stimulating pDCs than cells releasing mature virions. Additionally, cells replicating a release-deficient YFV mutant or a YFV subgenomic RNA lacking structural protein-coding sequences participated in pDC stimulation. Thus, viral RNAs produced by YFV-infected cells reach pDCs via at least two mechanisms: within immature particles and as capsid-free RNAs. Our work highlights the ability of pDCs to respond to a variety of vira...Continue Reading

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Citations

May 1, 2020·Journal of Biomolecular Structure & Dynamics·Raied A BadierahElrashdy M Redwan
May 27, 2020·Journal of Immunology Research·Patricio L AcostaLaura B Talarico
Apr 29, 2021·Human Vaccines & Immunotherapeutics·Amandine BovayDaniel E Speiser
May 1, 2021·International Journal of Molecular Sciences·Alessandra RossiSilvia Piconese

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Methods Mentioned

BETA
flow cytometry
ELISA
confocal microscopy
transfection
in vitro transcription
PCR
Enzyme-Linked Immunosorbent Assay

Software Mentioned

Huygens Essentials
ICY

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