Determining Tropism and Mechanisms of Ebola Virus Entry in Placental Tissues

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: Hanora Anne Marie Van Ert
Organization: UNIVERSITY OF IOWA
Fiscal Year: 2024
Award: $40,604
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary/Abstract
 During pregnancy, viral infections in the mother may have catastrophic effects on her health, or on the
viability of the developing fetus. Recently, emerging pathogen outbreaks such as those involving Zika Virus
(ZIKV), SARS-CoV-2 or Ebola Virus (EBOV) have highlighted how understudied the role of the placenta is in
transmission of viral infections. This project specifically focuses on the cell tropism of EBOV during pregnancy.
Ebola Virus Disease (EVD) is caused by infection with EBOV or other members within the Ebolavirus genus.
During pregnancy, EVD results in loss of ~100% of fetuses or neonates with or without the additional loss of
the mother. Anecdotal data from EBOV outbreaks in Africa suggest that EBOV directly infects placental
tissues, thus transmitting virus to the fetal compartment, but rigorous experimental evaluation of placental
infection has not been performed; the tropism of EBOV for placental cells, mechanisms of cellular entry, and
route of infection from mother to fetus are currently unknown. Aim 1 will examine tropism of EBOV in placental
tissues. Further, as EBOV has been shown to bind to and internalize into many cell types via interactions with
phosphatidylserine (PS) receptors, Aim 2 studies will evaluate the role of three PS receptors on EBOV
infection of the placenta and fetus. These studies will be performed using two low containment EBOV model
viruses, rVSV-EBOV-GP-GFP and EBOV ΔVP30, that have been used extensively to understand filovirus
tropism and receptor usage. The knowledge gained from these rigorously designed studies will elucidate cell
populations within the placenta infected and important for fetal transmission as a first step toward
understanding the catastrophic pathogenesis of EVD in pregnancy. Additionally, this work will provide insights
for the development of therapeutic treatment options to improve the maternal and fetal outcomes of EVD.
 The experiences, techniques, mentoring, and concepts in this proposal were specifically tailored to Ms.
Hanora Van Ert and her training goals. As a developing researcher passionate about improving the health and
wellbeing of pregnant women, Ms. Van Ert is currently completing her studies in the MSTP at University of
Iowa under the scientific mentorship of Dr. Wendy Maury and Dr. Mark Santillan receiving individualized
training at the intersection of virology, immunology, and reproductive health sciences to supply her passion
with the necessary research skills. Additionally, the MSTP, Department of OB/Gyn, and Department of
Microbiology and Immunology at the University of Iowa provide ample training opportunities in the forms of
seminar series, funding for attending academic conferences, opportunities to meet prominent people in the
fields of virology, immunology, and OB/Gyn, as well as a supportive and collaborative research environment.
Ms. Van Ert will complete her MSTP training and pursue a research residency in OB/Gyn, clinical Maternal-
fetal medicine fellowship, and ultimately tenure track position at an academic medical center to continue
investigating the host-pathogen immune response at the maternal-fetal interface within the placenta.

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