Defining the immune correlates of pathogenicity of Simian Hemorrhagic Fever virus in Rhesus macaques (P6314)

Abstract

Abstract The Clinical Laboratory at the Integrated Research Facility investigates correlates of immunity associated with lethality in nonhuman primates challenged with hemorrhagic fever viruses in high containment. In an intramuscular challenge study with simian hemorrhagic fever virus (SHFv) in rhesus macaques (Macaca mulatta) , we evaluated the factors associated with SHFv and opportunistic bacterial infections (e.g., abscesses) resulting from SHFv-induced immunosuppression. Elevated concentrations of the proinflammatory cytokines MCP-1 and IL-6 and severe septicemia were characteristic of most nonsurvivors of SHFv infection. Other factors associated with morbidity were elevated serum concentrations of AST, ALP, and ALT and decreased concentrations of albumin. Electron microscopy indicated that macrophages and endothelial cells were preferentially infected. Follow up in-vitro studies of SHFV-infected dendritic cells by immunophenotyping demonstrated that mature HLA-DR+ CD163+ cells were rapidly ablated within 48 h of infection with SHFV. Infection with SHFV, a biosafety level-2 (BSL-2) agent, is strikingly similar to infection with Ebola virus, a BSL-4 agent, in hemorrhagic presentation, clinical manifestations, and cellular targets. Further investigation is needed to elucidate the mechanisms of pathogenicity of SHFV infection, compare pathogenic pathways of these hemorrhagic fever virus infections, and identify therapeutic modalities for treatment of viral hemorrhagic fevers.