Högskolan i Skövde

Rift Valley Fever Virus (RVFV) is a Mosquito borne virus (Bunyaviridae family) associated withhemorrhagic fever and abortion in ruminants and humans. Geographic distribution of the virus has expanded to most countries in African continent and in 2001 to Arabian Peninsula resulting in repeated epidemic and epizootic events. With abortion being the hallmark of RVFV infection,Understanding RVFV infection in human placental tissue can provide better insight into disease pathobiology.

In this study, three human trophoblast cell lines (A3, Jar & BeWo) were evaluated for permissiveness to RVFV infection. Furthermore, the viral capacity to spread by producing progeny viruses in trophoblasts was evaluated. The trophoblast response to infection was additionally assessed by measuring expression levels of important inflammatory cytokines in the cells (IL-1 β, IL-6, IL-8, IL-10, IL15, CSF-2, IFN-g, Fas-L). Finaly, two viral entrance mechanisms suggested for this virus were investigated in these cell models.

Results suggested high permissiveness of studied trophoblasts cell lines to RVFV, leading to severe cytokine response (IL-8 and IL-1β in Jar and increase in CSF-2, IL-1β, IL-6 and IL-8 in A3 cell line). Since these cytokines are vital in embryonic regulation and development, the severe effect of infection could potentially be part of pathogenesis of virus-induced abortion. When viral entry routes were investigated, heparan sulfate proved to be the main cell entry membrane protein used by RVFV. However removal of all galactosylamintransferases resulted in higher infection rate suggesting presence of other entry mechanisms in absence of galactosylamin transferase. Considering these results and the nature of primary trophoblasts in resisting infection, it is important to evaluate if the primary trophoblasts show the same or similar pattern of sensitivity to RVFV infection with both wild type and mutated viral strains.These findings merit further investigations regarding pregnancy response to infection, vaccination and treatment.