Dissecting placental host-pathogen interactions: Rift Valley fever virus infection in early human trophoblast stem cells.
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Gwon YD, Haider S, Knöfler M, Bradley M, Henriksson J, Evander M
iScience 29 (5) 115584 [2026-05-15; online 2026-04-03]
Rift Valley fever virus (RVFV) is a mosquito-borne Phlebovirus and zoonotic pathogen affecting maternal-fetal health. Vertical transmission is linked to miscarriage and severe fetal outcomes, but mechanisms of placental pathogenesis remain unclear. We used first-trimester human trophoblast stem cells (hTSCs) to model infection at the maternal-fetal interface. Immunofluorescence, qRT-PCR, western blotting, and single-cell transcriptomics showed that hTSCs are highly susceptible to RVFV. Strand-specific viral transcriptomics confirmed the ambisense S segment and revealed preferential transcription of the M and S segments over L. RVFV induced G1 arrest, impairing trophoblast proliferation and differentiation, and drove widespread transcriptional reprogramming, including strong interferon lambda 1 (IFNL1) but modest type I interferon responses, and dysregulation of inflammatory and preeclampsia-associated genes such as RUNX1 and TGFBRAP1. Recombinant IFN-λ pretreatment reduced RVFV protein expression, highlighting hTSCs as a robust model and IFN-λ as a promising antiviral strategy.
NGI Stockholm (Genomics Production) [Service]
National Genomics Infrastructure [Service]
PubMed 42023155
DOI 10.1016/j.isci.2026.115584
Crossref 10.1016/j.isci.2026.115584
pmc: PMC13098504
pii: S2589-0042(26)00959-4