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Summary:
Researchers identified a novel SINE RNA-mediated mechanism that regulates endogenous Type III interferon (IFN-λ) signaling and antiviral defense at the maternal-fetal interface. Human syncytiotrophoblasts are uniquely resistant to viral infection and constitutively produce Type III interferons, even in the absence of pathogen exposure. This work elucidates a key molecular pathway underlying this intrinsic antiviral state, revealing SINE RNAs as previously unrecognized regulators of placental innate immunity.
The team demonstrated that SINE RNA transcripts embedded within the primate-specific C19MC and rodent-specific C2MC microRNA loci induce a viral mimicry response that activates Type III interferon production and antiviral protection in hemochorial placentas. In cellular and animal studies, loss of C2MC-associated SINE activity impaired antiviral defense, while SINE overexpression restored viral resistance. These findings establish a novel therapeutic target and provide the basis for developing RNA-based approaches to prevent or treat infection during pregnancy, enhance tissue-specific antiviral immunity, and potentially enable broader immune-modulating applications.
Fig 1 In vitro, C2MC knockout (Δ/Δ) mouse trophoblast stem (mTS) cells, and in vivo, C2MCΔ/Δ placentas, both exhibit a loss of their inherent IFNL3 expression and associated antiviral protection. However, the introduction of B1 SINE overexpression successfully reinstated viral resistance in C2MCΔ/Δ mTS cells.
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