Conserved pathogenesis of ancestral and contemporary Oropouche virus strains in a murine pregnancy model

Abstract

Abstract Oropouche virus (OROV) is an emerging orthobunyavirus responsible for widespread outbreaks across South and Central America. Recent reports of congenital disease have raised urgent concerns regarding the potential risk of OROV infection during pregnancy. Here, we establish an in vivo murine model of OROV vertical transmission using the ancestral (prototype) strain BeAn19991 in immunocompetent C57BL/6 J mice. We demonstrate that OROV robustly replicates in maternal tissues and efficiently infects the placenta. Complementary studies in human trophoblast-derived cell lines demonstrate conserved placental tropism across both the ancestral strain and a contemporary (outbreak) isolate, supporting the translational relevance of our findings. Notably, comparison of ancestral and contemporary viruses indicates that placental infection is not a recently acquired property of OROV. Further, offspring born to infected dams exhibit maternally derived neutralizing antibodies and transient protection upon postnatal challenge. Together, these findings, considered alongside emerging epidemiological evidence, identify pregnancy as a critical context for OROV infection and underscore the need to evaluate risks to pregnant individuals in endemic regions.