SFTSV NSs protein is a tick antiviral RNAi response suppressor
Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phenuivirus causing high mortality in humans. While the nonstructural protein NSs is dispensable for replication in interferon-deficient mammalian cells, we demonstrate that NSs is essential for viral replication in tick cells. SFTSV infection triggers canonical Dicer-2-mediated antiviral RNA interference (RNAi) in tick cells, producing virus-derived small interfering RNAs (siRNAs) that target viral transcripts for degradation. We show that NSs functions as a viral suppressor of RNAi by selectively engaging and depleting single-stranded RNAs derived from 22-nucleotide siRNAs, likely limiting their incorporation into RNA-induced silencing complexes (RISC). Complementation with a heterologous RNAi suppressor (p19 protein) partially rescues replication of NSs-deficient virus, validating the RNAi-suppressive function of NSs. These findings reveal that successful tick-borne viral replication requires host-specific immune evasion strategies and establish NSs-mediated RNAi suppression as essential for SFTSV persistence in arthropod vectors.
Authors
- Marine J. Petit (ORCID: https://orcid.org/0000-0001-7427-7203)
- Andrew T. Clarke (ORCID: https://orcid.org/0000-0001-7271-3833)
- Esther Schnettler (ORCID: https://orcid.org/0000-0001-8141-3728)
- Kelsey Davies (ORCID: https://orcid.org/0009-0009-5624-5983)
- Alfredo Castelló (ORCID: https://orcid.org/0000-0002-1499-4662)
- Ulrich Schwarz‐Linek (ORCID: https://orcid.org/0000-0003-0526-223X)
- Benjamin Brennan (ORCID: https://orcid.org/0000-0003-4707-726X)
- Melanie McFarlane
- Rozeena Arif (ORCID: https://orcid.org/0009-0007-0492-6352)
- Riona Datta-Savage (ORCID: https://orcid.org/0009-0001-3718-0733)
- Lesley Bell-Sakyi (ORCID: https://orcid.org/0000-0002-7305-0477)
- Alain Kohl (ORCID: https://orcid.org/0000-0002-1523-9458)
- Wael Kamel (ORCID: https://orcid.org/0000-0002-7625-2648)
- Rhys H. Parry (ORCID: https://orcid.org/0000-0001-9238-1952)
- Mazigh Fares (ORCID: https://orcid.org/0000-0002-6003-9244)
Institutions
- University of Liverpool (GB)
- Universität Hamburg (DE)
- The University of Queensland (AU)
- University of St Andrews (GB)
- Liverpool School of Tropical Medicine (GB)
- German Center for Infection Research (DE)
- MRC University of Glasgow Centre for Virus Research (GB)
- Institute of Infection and Immunity (CA)
- HAW Hamburg (DE)
- Medical Research Council (GB)
- Bernhard Nocht Institute for Tropical Medicine (DE)
Publication Details
- Journal
- Proceedings of the National Academy of Sciences
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1073/pnas.2524728123
- Primary Topic
- Viral Infections and Vectors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsches Zentrum für Infektionsforschung
- Wellcome Trust
- Horizon 2020 Framework Programme
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- European Research Council
- Medical Research Future Fund