Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis
| العنوان: | Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis |
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| المؤلفون: | Joshua D. Shamblin, Kayla M. Coffin, Darci R. Smith, Matt A. Voorhees, Jeffrey W. Koehler, Xiankun Zeng, Jun Liu, Franco Rossi, Connie S. Schmaljohn, Christopher W. Schellhase, Adrienne E. Kimmel, Charles J. Shoemaker, Justine M. Zelko, Keersten M. Ricks, William D. Pratt, Collin Fitzpatrick, Aura R. Garrison, Randal J. Schoepp, Joseph W. Golden, Olivier Flusin |
| المصدر: | PLoS Pathogens PLoS Pathogens, Vol 15, Iss 9, p e1008050 (2019) |
| بيانات النشر: | Public Library of Science, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Crimean–Congo hemorrhagic fever, Male, Physiology, Fevers, Monkeys, Pathology and Laboratory Medicine, Antibodies, Viral, Communicable Diseases, Emerging, Animal Cells, Immune Physiology, Testis, Biology (General), Neglected tropical diseases, Mammals, 0303 health sciences, Innate Immune System, Granuloma, biology, Latent tuberculosis, 030302 biochemistry & molecular biology, Eukaryota, Hematology, 3. Good health, Actinobacteria, Vertebrates, Hemorrhagic Fever Virus, Crimean-Congo, Granulomas, Disease Progression, Crimean-Congo hemorrhagic fever, Infectious diseases, Cytokines, Viral disease, Cellular Types, Crimean Congo hemorrhagic fever virus, Macaque, Research Article, Primates, Tuberculosis, QH301-705.5, Immune Cells, Immunology, Viremia, Viral diseases, Microbiology, Virus, Mycobacterium tuberculosis, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Latent Tuberculosis, Virology, Old World monkeys, Genetics, medicine, Animals, Humans, Molecular Biology, 030304 developmental biology, Medicine and health sciences, Biology and life sciences, Bacteria, Host Microbial Interactions, Tropical diseases, Organisms, Cell Biology, RC581-607, Molecular Development, medicine.disease, biology.organism_classification, Disease Models, Animal, Macaca fascicularis, Immune System, Amniotes, Parasitology, Hemorrhagic Fever, Crimean, Immunologic diseases. Allergy, Viral hemorrhagic fevers, Mycobacterium Tuberculosis, Developmental Biology |
| الوصف: | 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. Author summary CCHF is an emerging tick-borne viral disease that is endemic across much of Africa and Asia, and parts of Europe where its range and exposure risk to human populations is expanding. Tuberculosis threatens millions of lives world-wide and is the leading cause of death due to a bacterial pathogen. Concurrent mycobacterial infection with other infectious diseases has been described, but not for CCHFV despite the geographic overlap of these two pathogens. During our study we unexpectedly determined that some of the animals had latent tuberculosis and that CCHFV can persist within the granulomas. Furthermore, our study provides the first direct evidence that CCHFV can replicate and persist in the male genital tract, which has important implications for human sexual transmission. The ability of viral RNA to persist in immune-privileged sites or fluids has been described with increasing frequency for other emerging infectious diseases and can cause a burden on public health. This provides the impetus to utilize the model described here to better understand the mechanisms of CCHFV persistence and its effect on the development of long-term sequelae. |
| اللغة: | English |
| تدمد: | 1553-7374 1553-7366 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d4640bcdb2ad845388aeb0eed7660ccb http://europepmc.org/articles/PMC6782109 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....d4640bcdb2ad845388aeb0eed7660ccb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15537374 15537366 |
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