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Virus infections as the cause of miscarriages and malformations: Tropism and Mechanisms

Research project financed by the Swedish Research Council.

The aim with the project is to characterize the pathogenesis of vertical viral infections.

Head of project

Project overview

Project period:

2023-01-01 2026-12-31

Participating departments and units at Umeå University

Department of Clinical Microbiology, Umeå Centre for Microbial Research (UCMR)

Research area

Infection biology

Project description

Infection with Rift Valley fever virus (RVFV) cause mass abortions in livestock and is associated with miscarriage in humans. The candidate RVFV vaccine strains MP12 and clone 13, both with a non-functional RVFV NSs-gene, have teratogenic effects. Virus infection pathways in the fetus and host protective mechanisms, e.g. by the innate immune system, are poorly understood. For vertical transmission of RVFV, little work has been done outside of livestock, and then mostly centered around safety of live-attenuated vaccines rather than a deeper understanding the mechanism of trans-placental infection. Thus, there is a major gap in the field in understanding how viruses in general, and RVFV, are transmitted from mother to fetus.

We will characterize RVFV tropism and the inflammatory response in human and rodent placental cells for wildtype and NSs deleted RVFV, respectively. We will study the infection process, antiviral and cytokine response in vitro, in early-stage and late-stage trophoblasts, as well as perform infection experiments in a mouse model. In preliminary studies, we have established 2D and 3D-human stem cell cultures, and we show that trophoblast cell lines and human placental stem cells are infected by RVFV.

Our research will provide novel information on pathogenesis of vertically transmitted RVFV and add to the general understanding of fetal infections for other viruses. RVFV is a prioritized disease listed by WHO for urgent research and development of counteraction.

 

Latest update: 2023-02-02