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Viruses 2019, 11(1), 67; https://doi.org/10.3390/v11010067

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

1
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
2
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
3
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
4
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
5
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 3170 UW Medical Foundation Centennial Building, 1685 Highland Ave, Madison, WI 53711, USA
6
Wisconsin National Primate Research Center, Southwest Commuter Path, Madison, WI 53711, USA
*
Author to whom correspondence should be addressed.
Present address: One MedImmune Way, Gaithersburg, MD 20878, USA.
Present address: Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, 660 S. Euclid Ave, St. Louis, MO 63110, USA.
§
Present address: Mapp Biopharmaceutical, Inc., 6160 Lusk Blvd. # C105, San Diego, CA 92121, USA.
Received: 8 November 2018 / Revised: 27 December 2018 / Accepted: 11 January 2019 / Published: 15 January 2019
(This article belongs to the Section Animal Viruses)
Full-Text   |   PDF [6461 KB, uploaded 15 January 2019]   |  

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. View Full-Text
Keywords: Arteriviridae; arterivirus; host response; macaque; patas monkey; pathogenesis; SHFV; simarterivirus; simian hemorrhagic fever; viral hemorrhagic fever Arteriviridae; arterivirus; host response; macaque; patas monkey; pathogenesis; SHFV; simarterivirus; simian hemorrhagic fever; viral hemorrhagic fever
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Cornish, J.P.; Moore, I.N.; Perry, D.L.; Lara, A.; Minai, M.; Promeneur, D.; Hagen, K.R.; Virtaneva, K.; Paneru, M.; Buechler, C.R.; O’Connor, D.H.; Bailey, A.L.; Cooper, K.; Mazur, S.; Bernbaum, J.G.; Pettitt, J.; Jahrling, P.B.; Kuhn, J.H.; Johnson, R.F. Clinical Characterization of Host Response to Simian Hemorrhagic Fever Virus Infection in Permissive and Refractory Hosts: A Model for Determining Mechanisms of VHF Pathogenesis. Viruses 2019, 11, 67.

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