Host response to Rift Valley fever virus infection

Rift Valley fever virus (RVFV) has the ability to cause severe disease (in the form of encephalitis or hemorrhagic fever) in humans and animals. RVFV is endemic to parts of Africa and the Arabian Peninsula, but there is significant concern regarding its potential introduction into non-endemic regions and the potentially devastating effect to livestock populations with concurrent infections of humans. The lack of licensed vaccines or therapeutics contributes to the designation of RVFV as a category A agent on the NIAID list of priority pathogens. During outbreaks in livestock, a nearly 100% abortion rate in infected pregnant animals can be observed with up to a 60% mortality rate in adult animals. Until recently, limited information has been published on the host response to infection by RVFV. To date, there is little detailed data directly comparing the host response to infection with RVFV and correlation with viral pathogenesis. My goal was to be able to discern the host response to infection and to correlate the response with development of RVFV-induced pathogenesis. My efforts have centered on understanding how host immune-modulatory cells respond to infection.
In the first part of my project, primary mouse bone marrow derived (BMD) macrophages were infected with MP-12 (attenuated vaccine strain), rMP-12 Clone13 type virus (a recombinant virus resembling a naturally occurring attenuated strain), and ZH501 (pathogenic wild type strain). The cytokines and chemokines examined show a larger increase after MP-12 or rMP12-C13type infection when compared to the increase of the same cytokines after ZH501 infection. Since ZH501 does not induce secretion of cytokines in macrophage cells, it may be using these cells for transport and as initial replication site. The second part of my project involved characterizing clinical and systemic immune responses to infection with ZH501 or MP-12 in the C57BL/6 mouse. Animals infected with MP-12 survived productive viral infection with little evidence of clinical disease and minimal cytokine response in evaluated tissues. In contrast, ZH501 infection was lethal, caused depletion of lymphocytes and platelets and elicited a strong, systemic cytokine response which correlated with high virus titers and significant tissue pathology.