Pathogenesis of Aerosolized Ebola Virus Variant Makona in Nonhuman Primates.

Autor:	Prasad AN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Fenton KA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Agans KN; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Borisevich V; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Woolsey C; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Comer JE; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Dobias NS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Peel JE; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Deer DJ; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Geisbert JB; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Lawrence WS; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Cross RW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA., Geisbert TW; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.; Galveston National Laboratory, University of Texas Medical Branch, Galveston, Texas, USA.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2023 Nov 13; Vol. 228 (Suppl 7), pp. S604-S616.
DOI:	10.1093/infdis/jiad137
Abstrakt:	Background: Highly pathogenic filoviruses such as Ebola virus (EBOV) hold capacity for delivery by artificial aerosols, and thus potential for intentional misuse. Previous studies have shown that high doses of EBOV delivered by small-particle aerosol cause uniform lethality in nonhuman primates (NHPs), whereas only a few small studies have assessed lower doses in NHPs. Methods: To further characterize the pathogenesis of EBOV infection via small-particle aerosol, we challenged cohorts of cynomolgus monkeys with low doses of EBOV variant Makona, which may help define risks associated with small particle aerosol exposures. Results: Despite using challenge doses orders of magnitude lower than previous studies, infection via this route was uniformly lethal across all cohorts. Time to death was delayed in a dose-dependent manner between aerosol-challenged cohorts, as well as in comparison to animals challenged via the intramuscular route. Here, we describe the observed clinical and pathological details including serum biomarkers, viral burden, and histopathological changes leading to death. Conclusions: Our observations in this model highlight the striking susceptibility of NHPs, and likely humans, via small-particle aerosol exposure to EBOV and emphasize the need for further development of diagnostics and postexposure prophylactics in the event of intentional release via deployment of an aerosol-producing device. Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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