Mary Wilson
Well-known member
Published: 22 June 2023
https://doi.org/10.1093/infdis/jiad225
Abhishek N Prasad, Krystle N Agans, Joan B Geisbert, Viktoriya Borisevich, Daniel J Deer, Natalie S Dobias, Jason E Comer, Courtney Woolsey, Karla A Fenton, Thomas W Geisbert ... Show more
Abstract
Background
The primary route of infection by Ebola virus (EBOV) and other pathogenic filoviruses in humans is through contact of contaminated body fluids with mucosal surfaces. Few studies have explored infection of nonhuman primates (NHPs) via the oral mucosa, which is a probable portal of natural infection in humans.
Methods
To further characterize the pathogenesis of EBOV infection via the oral exposure route, we challenged cohorts of cynomolgus monkeys with low doses (100 PFU, 50 PFU, 10 PFU) of EBOV variant Makona to better characterize virus infection and the host immune response via this route.
Results
Infection with 100 or 50 PFU of EBOV Makona via the oral route resulted in 50% and 83% lethality, respectively. Animals that progressed to fatal disease exhibited lymphopenia, marked coagulopathy, high viral loads, and increased levels of serum markers of inflammation and hepatic/renal injury. Survival in these cohorts was associated with milder fluctuations in leukocyte populations, a lack of coagulopathy, and reduced or absent serum markers of inflammation and/or hepatic/renal function. Surprisingly, two surviving animals from the 100 and 50 PFU cohorts developed transient low-level viremia in the absence of other clinical signs of disease. Conversely, all animals in the 10 PFU cohort remained disease free and survived to the study endpoint.
Conclusions
Our observations highlight the susceptibility of NHPs, and by extension, likely humans, to relatively low doses of EBOV via the oral route. As this route of infection is likely a common portal of entry for filoviruses during outbreaks, the data presented here add to our understanding of the pathogenesis and host-response to infection under conditions mimicking real-world scenarios.
https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiad225/7205316
https://doi.org/10.1093/infdis/jiad225
Abhishek N Prasad, Krystle N Agans, Joan B Geisbert, Viktoriya Borisevich, Daniel J Deer, Natalie S Dobias, Jason E Comer, Courtney Woolsey, Karla A Fenton, Thomas W Geisbert ... Show more
Abstract
Background
The primary route of infection by Ebola virus (EBOV) and other pathogenic filoviruses in humans is through contact of contaminated body fluids with mucosal surfaces. Few studies have explored infection of nonhuman primates (NHPs) via the oral mucosa, which is a probable portal of natural infection in humans.
Methods
To further characterize the pathogenesis of EBOV infection via the oral exposure route, we challenged cohorts of cynomolgus monkeys with low doses (100 PFU, 50 PFU, 10 PFU) of EBOV variant Makona to better characterize virus infection and the host immune response via this route.
Results
Infection with 100 or 50 PFU of EBOV Makona via the oral route resulted in 50% and 83% lethality, respectively. Animals that progressed to fatal disease exhibited lymphopenia, marked coagulopathy, high viral loads, and increased levels of serum markers of inflammation and hepatic/renal injury. Survival in these cohorts was associated with milder fluctuations in leukocyte populations, a lack of coagulopathy, and reduced or absent serum markers of inflammation and/or hepatic/renal function. Surprisingly, two surviving animals from the 100 and 50 PFU cohorts developed transient low-level viremia in the absence of other clinical signs of disease. Conversely, all animals in the 10 PFU cohort remained disease free and survived to the study endpoint.
Conclusions
Our observations highlight the susceptibility of NHPs, and by extension, likely humans, to relatively low doses of EBOV via the oral route. As this route of infection is likely a common portal of entry for filoviruses during outbreaks, the data presented here add to our understanding of the pathogenesis and host-response to infection under conditions mimicking real-world scenarios.
https://academic.oup.com/jid/advance-article-abstract/doi/10.1093/infdis/jiad225/7205316