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NIH grant 1R21AI193850-01A1: Vertical Transmission of Past and Present Oropouche Virus Isolates: Comparing Tropism and Pathogenesis using Human Ex Vivo and Rodent in Vivo Models
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Cynthia Marie McMillen. Award: $234262.
Start: 2026-08-06T00:00:00.
PROJECT SUMMARY: Vertical transmission of past and present Oropouche virus
isolates: Comparing tropism and pathogenesis using human ex vivo and rodent in vivo
models.
Oropouche virus (OROV) is an emerging bunyavirus with epidemic potential. The 2024 OROV
outbreak has revealed a previously unrecognized diversity of clinical outcomes including adult
fatalities, cases of vertical transmission, and adverse outcomes in newborns including
microcephaly, still-birth and neonatal deaths. There are major gaps in our understanding of
OROV pathogenesis and there are no vaccines or therapeutics to mitigate disease. Given the
recent first reports of vertical transmission, we seek to understand how OROV is transmitted
from mother to offspring and to define its potential impact on maternal and fetal health. Here, we
propose to leverage our experience studying vertical transmission of a related bunyavirus, Rift
Valley fever virus, and re-establish ex vivo and in vivo models to study OROV vertical
transmission. Genomic reassortment may be associated with this perceived change in tropism
and virulence, therefore we aim to investigate differences in vertical transmission between four
strains (BeAn19991, BeH759021, LET2083, AM0088) representing four genetically distinct
lineages of OROV (OROVBR/TT 1955-2003, OROVBR 2009-2018, OROVPE/CO/EC 2008-2021, OROVBR 2015-2024,
respectively). This work will be performed by highly productive and collaborative investigators
with expertise in every aspect of the proposed studies, including bunyavirus pathogenesis,
immunology, virology, histopathology, and the use of models of the maternal-fetal interface.
Completion of these studies will provide valuable information regarding OROV vertical
transmission and lay the groundwork for future studies identifying genetic and molecular
changes to OROV that contribute to vertical transmission or fetal demise. We expect to identify
strain-specific tropisms, pathologies, and host responses at the maternal-fetal interface that is
validated across multiple models, providing well-characterized models to test therapeutics and
vaccines.document fetched 2026-08-15 06:35