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

Infection with Rift Valley fever virus (RVFV) is associated with miscarriage in humans and cause mass abortions in livestock.

The candidate RVFV vaccine strains MP12 and clone 13, both with a non-functional virulence RVFV NSs-gene, still have teratogenic effects.

Virus infection pathways in the fetus and host protective mechanisms, e.g. by the innate immune system, are poorly understood.

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 determine RVFV tropism and the inflammatory response in human placental cells for wild-type and NSs deleted RVFV.

Both in early-stage and late-stage human placental cells, we will study the infection process, antiviral and cytokine response, as well as gene expression by single cell RNA sequencing. In addition, we will use our assays to study other vertically transmitted mosquito-borne viruses. RVFV infection during pregnancy will also be characterized 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 ,and cause a pro-inflammatory cytokine response.

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.