Vaccine Strains of Rift Valley Fever Virus Exhibit Attenuation at the Maternal-fetal Placental Interface

Overview

Journal bioRxiv

Date 2024 Jun 10

PMID 38854055

Authors

Cynthia M McMillen

Christina Megli

Rebecca Radisic

Lauren B Skvarca

Ryan M Hoehl

Devin A Boyles

Jackson J McGaughey

Brian H Bird

Anita K McElroy

Amy L Hartman

Affiliations

Soon will be listed here.

Abstract

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal-fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent in the maternal-facing side. Type-I and type-III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal-fetal interface.

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