Porcine macrophage-like cells permit viral replication, produce inflammatory mediators, and undergo apoptosis following infection with Rift Valley fever virus MP-12

Abstract

Abstract Rift Valley fever virus (RVFV) is a mosquito-borne virus that can cause severe disease in a variety of domestic animal species as well as in humans. Outbreaks occur primarily in Sub-Saharan Africa with ruminant livestock most affected and outcomes that include abortion storms and high mortality among young animals. Clinical disease is not known to occur in domestic pigs (Sus scrofa); however, a limited number of studies have detected circulating antibodies to RVFV among wild and domestic members of the pig family (Suidae). Experimentally, RVFV has been shown to replicate in some porcine epithelial and neuronal cells in vitro, and induce a viremia in a fraction of pigs inoculated in vivo. No studies to date have investigated the behavior of RVFV in porcine cells of immune origin, whereas in humans and mice, macrophages and dendritic cells have been implicated as having roles in RVFV pathogenicity. Here, we use a porcine monocyte-derived macrophage-like cell line, CΔ2+, to investigate porcine innate immune cell permissiveness to MP-12, an attenuated form of RVFV. MP-12 caused observable cytopathic effects in CΔ2+ cells and reduced cell viability in dose- and time-dependent manners. At 24 hours, the reduced viability was coincident with apoptosis, with necrosis also occurring at a higher multiplicity of infection. At early time points, MP-12 replicated at levels comparable to cells derived from sheep kidney—a target organ of a highly susceptible host species. Infected CΔ2+ cells also upregulated transcription of inflammatory mediators. This work provides the first evidence that porcine immune cells are permissive to RVFV, and indicates that additional studies are warranted to better understand the dynamics of RVFV in suids.