Modeling Challenges of Ebola Virus–Host Dynamics during Infection and Treatment

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.

Lassa viral dynamics in non-human primates treated with favipiravir or ribavirin

“…First, we assumed that LASV infection occurred only in one compartment. Although this may raise criticism [35], modeling multicompartmental infection will require data that do not exist at this time. We took the liver size as a proxy for the number of infected cells, which is supported by necropsy sampling showing that the liver was the organ having the highest level of viral replication (S8 Fig).…”

Modeling suggests that virion production cycles within individual cells is key to understanding acute hepatitis B virus infection kinetics

“…Standard population-based measurements of viral infection time courses typically show an initial eclipse phase followed by exponential increase ending either in cell lysis or steady state viral levels [13][14][15][16][17][18][19][20][21]. However, we recently reported a surprising complex HBV infection kinetics in chimeric uPA-SCID mice with humanized livers [9].…”

Quantification of Ebola virus replication kinetics in vitro

“…Nevertheless, our findings have some relevance to understanding the EBOV infection in vivo . EBOV initially replicates within macrophages and dendritic cells in subcutaneous and submucosal compartments, but dissemination in the blood results in the infection of multiple organs throughout the body [ 40 ]. Many different cell types are infected with varying susceptibility to infection, as well as varying levels of viral replication.…”