Abstract
Mathematical modeling of Ebola virus (EBOV)–host dynamics during infection and treatment in vivo is in its infancy due to few studies with frequent viral kinetic data, lack of approved antiviral therapies, and limited insight into the timing of EBOV infection of cells and tissues throughout the body. Current in-host mathematical models simplify EBOV infection by assuming a single homogeneous compartment of infection. In particular, a recent modeling study assumed the liver as the largest solid organ targeted by EBOV infection and predicted that nearly all cells become refractory to infection within seven days of initial infection without antiviral treatment. We compared our observations of EBOV kinetics in multiple anatomic compartments and hepatocellular injury in a critically ill patient with Ebola virus disease (EVD) with this model’s predictions. We also explored the model’s predictions, with and without antiviral therapy, by recapitulating the model using published inputs and assumptions. Our findings highlight the challenges of modeling EBOV–host dynamics and therapeutic efficacy and emphasize the need for iterative interdisciplinary efforts to refine mathematical models that might advance understanding of EVD pathogenesis and treatment.
| Original language | English |
|---|---|
| Article number | 106 |
| Journal | Viruses |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - 16 Jan 2020 |
| Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020 by the authors.
Funding
Funding: This research was funded in part by the U.S. National Institute of Health (NIH) Intramural Research Program, and NIH grants R01AI144112, R01-AI078881 and R01GM121600. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Critical Care Medicine Department, National Institutes of Health Clinical Center, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA The Program for Experimental and Theoretical Modeling, Division of Hepatology, Department of Medicine, Loyola University Medical Center, Maywood, IL 60153, USA; [email protected] (L.S.); [email protected] (H.D.) Network Science Institute, Northeastern University, Boston, MA 02115, USA Liver Unit, Shaare Zedek Medical Center and the Hebrew University of Jerusalem, Jerusalem 9103102, Israel; [email protected] Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] Translational Hepatology Unit, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] Correspondence: [email protected]; Tel.: +1-(301)-451-7731 This research was funded in part by the U.S. National Institute of Health (NIH) Intramural Research Program, and NIH grants R01AI144112, R01-AI078881 and R01GM121600. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
| Funders | Funder number |
|---|---|
| Critical Care Medicine Department | |
| Department of Medicine | |
| Laboratory of Immunoregulation | |
| National institute of Health | |
| U.S. Government | |
| U.S. National Institute of Health | |
| National Institutes of Health | R01GM121600 |
| U.S. Department of Health and Human Services | |
| National Institute of Allergy and Infectious Diseases | R01AI078881, R01AI144112 |
| National Institute of Diabetes and Digestive and Kidney Diseases | |
| NIH Clinical Center | |
| Northeastern University | |
| Hebrew University of Jerusalem |
Keywords
- Ebola virus
- Liver
- Mathematical modeling
- Viral kinetics
