Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis
Joseph P. Cornish,
Ian N. Moore,
Donna L. Perry,
Abigail Lara,
Mahnaz Minai,
Dominique Promeneur,
Katie R. Hagen,
Kimmo Virtaneva,
Monica Paneru,
Connor R. Buechler,
David H. O’Connor,
Adam L. Bailey,
Kurt Cooper,
Steven Mazur,
John G. Bernbaum,
James Pettitt,
Peter B. Jahrling,
Jens H. Kuhn,
Reed F. Johnson
Affiliations
Joseph P. Cornish
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Ian N. Moore
Infectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA
Donna L. Perry
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Abigail Lara
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Mahnaz Minai
Infectious Disease Pathogenesis Section, Comparative Medicine Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA
Dominique Promeneur
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Katie R. Hagen
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Kimmo Virtaneva
Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA
Monica Paneru
Genomics Unit, Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT 59840, USA
Connor R. Buechler
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave, Madison, WI 53711, USA
David H. O’Connor
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave, Madison, WI 53711, USA
Adam L. Bailey
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave, Madison, WI 53711, USA
Kurt Cooper
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Steven Mazur
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
John G. Bernbaum
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
James Pettitt
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Peter B. Jahrling
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Jens H. Kuhn
Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
Reed F. Johnson
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Fort Detrick, Frederick, MD 21702, USA
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.
