Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacteria...

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Published in:	PLoS pathogens Vol. 15; no. 9; p. e1008050
Main Authors:	Smith, Darci R, Shoemaker, Charles J, Zeng, Xiankun, Garrison, Aura R, Golden, Joseph W, Schellhase, Christopher W, Pratt, William, Rossi, Franco, Fitzpatrick, Collin J, Shamblin, Joshua, Kimmel, Adrienne, Zelko, Justine, Flusin, Olivier, Koehler, Jeffrey W, Liu, Jun, Coffin, Kayla M, Ricks, Keersten M, Voorhees, Matt A, Schoepp, Randal J, Schmaljohn, Connie S
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 26-09-2019 Public Library of Science (PLoS)
Subjects:	Analysis Animal models Animals Antibodies, Viral - blood Armed forces Bacterial infections Biology and life sciences Communicable Diseases, Emerging - complications Communicable Diseases, Emerging - pathology Communicable Diseases, Emerging - virology Comorbidity Concurrent infection Crimean hemorrhagic fever Cytokines - blood Death Defense contracts Development and progression Disease Models, Animal Disease Progression Ebola virus Epidemics Fever Granuloma - microbiology Granuloma - pathology Granuloma - virology Granulomas Hematology Hemorrhage Hemorrhagic Fever Virus, Crimean-Congo - genetics Hemorrhagic Fever Virus, Crimean-Congo - immunology Hemorrhagic Fever Virus, Crimean-Congo - pathogenicity Hemorrhagic Fever, Crimean - complications Hemorrhagic Fever, Crimean - pathology Hemorrhagic Fever, Crimean - virology Hemorrhagic fevers Histochemistry Histopathology Host Microbial Interactions - immunology Humans Infections Infectious diseases Latent Tuberculosis - complications Latent Tuberculosis - microbiology Latent Tuberculosis - pathology Macaca fascicularis Male Medical research Medicine and health sciences Monkeys Organic chemistry Pathogenic microorganisms Pathogens Pathology Primates Public health RNA polymerase Smith, Charles Strains (organisms) Testis - microbiology Testis - pathology Testis - virology Tick-borne diseases Tuberculosis Viral diseases Viral infections Viremia Virology Virus diseases Viruses Asia Europe United States > US Maryland Africa
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Summary:	Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.
Bibliography:	new_version ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Immunodiagnostics Department, Biological Defense Research Directorate, Naval Medical Research Center, Ft. Detrick, MD, United States of America The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1008050