Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis

Abstract

Simian hemorrhagic fever virus (SHFV) causes a fulminant and typically lethal viral hemorrhagic fever (VHF) in macaques (Cercopithecinae: Macaca spp.) but causes subclinical infections in patas monkeys (Cercopithecinae: Erythrocebus patas). This difference in disease course offers a unique opportunity to compare host responses to infection by a VHF-causing virus in biologically similar susceptible and refractory animals. Patas and rhesus monkeys were inoculated side-by-side with SHFV. Unlike the severe disease observed in rhesus monkeys, patas monkeys developed a limited clinical disease characterized by changes in complete blood counts, serum chemistries, and development of lymphadenopathy. Viral RNA was measurable in circulating blood 2 days after exposure, and its duration varied by species. Infectious virus was detected in terminal tissues of both patas and rhesus monkeys. Varying degrees of overlap in changes in serum concentrations of interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6 were observed between patas and rhesus monkeys, suggesting the presence of common and species-specific cytokine responses to infection. Similarly, quantitative immunohistochemistry of livers from terminal monkeys and whole blood flow cytometry revealed varying degrees of overlap in changes in macrophages, natural killer cells, and T-cells. The unexpected degree of overlap in host response suggests that relatively small subsets of a host’s response to infection may be responsible for driving hemorrhagic fever pathogenesis. Furthermore, comparative SHFV infection in patas and rhesus monkeys offers an experimental model to characterize host–response mechanisms associated with viral hemorrhagic fever and evaluate pan-viral hemorrhagic fever countermeasures.

A Review on Zoonotic Pathogens Associated with Non-Human Primates: Understanding the Potential Threats to Humans

“…Adenovirus is a common virus in the respiratory and digestive tracts of monkeys. Some scholars have suggested that infection by SADV has strict species specificity, and there are reports of potential cross-transmission between NHP species [ 19 ]. SADV and human adenovirus are closely related and share a common soluble complement-binding antigen.…”

Development and Characterization of a cDNA-Launch Recombinant Simian Hemorrhagic Fever Virus Expressing Enhanced Green Fluorescent Protein: ORF 2b’ Is Not Required for In Vitro Virus Replication

“…Consequently, SHF pathogenesis due to SHFV infection has been characterized in greatest detail. SHF caused by SHFV presents with sudden onset of fever, anorexia, edema, dyspnea, diarrhea, lymphadenopathy, splenomegaly, hemorrhage, disseminated intravascular coagulation, liver and adrenal gland necrosis, lymphocyte depletion, and systemic shock [ 3 , 10 , 17 , 18 , 19 , 20 ]. SHFV initially targets macrophages but also has been detected in astrocytes, vascular endothelial cells, glial cells, and neuronal cell bodies [ 21 ].…”