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

Autoři: Darci R. Smith aff001;  Charles J. Shoemaker aff002;  Xiankun Zeng aff003;  Aura R. Garrison aff001;  Joseph W. Golden aff001;  Chris Schellhase aff003;  William Pratt aff001;  Franco Rossi aff001;  Collin J. Fitzpatrick aff001;  Joshua Shamblin aff001;  Adrienne Kimmel aff001;  Justine Zelko aff001;  Olivier Flusin aff002;  Jeffrey W. Koehler aff002;  Jun Liu aff003;  Kayla M. Coffin aff003;  Keersten M. Ricks aff002;  Matt A. Voorhees aff002;  Randal J. Schoepp aff002;  Connie S. Schmaljohn aff004
Působiště autorů: Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Maryland, United States of America aff001;  Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Maryland, United States of America aff002;  Pathology Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Maryland, United States of America aff003;  Headquarters Division, U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Maryland, United States of America aff004
Vyšlo v časopise: Persistent Crimean-Congo hemorrhagic fever virus infection in the testes and within granulomas of non-human primates with latent tuberculosis. PLoS Pathog 15(9): e32767. doi:10.1371/journal.ppat.1008050
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008050


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.

Klíčová slova:

Cytokines – Fevers – Hematology – Macaque – Crimean-Congo hemorrhagic fever – Granulomas – Viremia


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