TY - JOUR
T1 - Spatio-temporal dynamics of Host-Virus competition
T2 - A model study of influenza A
AU - Whitman, John
AU - Dhanji, Aleya
AU - Hayot, Fernand
AU - Sealfon, Stuart C.
AU - Jayaprakash, Ciriyam
N1 - Publisher Copyright:
© 2019
PY - 2020/1/7
Y1 - 2020/1/7
N2 - We present results of a study of the early-time response of the innate immune system to influenza virus infection in an agent-based model (ABM) of epithelial cell layers. We find that the competition between the anti-viral immune response and viral antagonism can lead to viral titers non-monotonic in the initial infection fraction as found in experiments. Our model includes a coarse-grained version of intra-cellular processes and inter-cellular communication via cytokine and virion diffusion. We use ABM to follow the propagation of viral infection in the layer and the increase of the viral load as a function of time for different values of the multiplicity of infection (MOI), the initial number of viruses added per cell. We find that for moderately strong host immune response, the number of infected cells and viral load for a smaller MOI exceeds that for larger MOI, as seen in experiments. We elucidate the mechanism underlying this result as the synergistic action of cytokines secreted by infected cells in controlling viral amplification for larger MOI. We investigate the length and time scales that determine this non-monotonic behavior within the ABM. We study the diffusive spread of virions and cytokines from a single infected cell in an absorbing medium analytically and numerically and deduce the length scale that yields a good estimate of the MOI at which we find non-monotonicity. Detailed computations of the temporal behavior of averaged quantities and spatial measures provide further insights into host-viral interactions and connections to experimental observations.
AB - We present results of a study of the early-time response of the innate immune system to influenza virus infection in an agent-based model (ABM) of epithelial cell layers. We find that the competition between the anti-viral immune response and viral antagonism can lead to viral titers non-monotonic in the initial infection fraction as found in experiments. Our model includes a coarse-grained version of intra-cellular processes and inter-cellular communication via cytokine and virion diffusion. We use ABM to follow the propagation of viral infection in the layer and the increase of the viral load as a function of time for different values of the multiplicity of infection (MOI), the initial number of viruses added per cell. We find that for moderately strong host immune response, the number of infected cells and viral load for a smaller MOI exceeds that for larger MOI, as seen in experiments. We elucidate the mechanism underlying this result as the synergistic action of cytokines secreted by infected cells in controlling viral amplification for larger MOI. We investigate the length and time scales that determine this non-monotonic behavior within the ABM. We study the diffusive spread of virions and cytokines from a single infected cell in an absorbing medium analytically and numerically and deduce the length scale that yields a good estimate of the MOI at which we find non-monotonicity. Detailed computations of the temporal behavior of averaged quantities and spatial measures provide further insights into host-viral interactions and connections to experimental observations.
KW - Agent-based modeling
KW - Epithelial cells
KW - Innate immune system
KW - Modeling flu
KW - Multiplicity of infection
KW - Stochastic modeling
UR - http://www.scopus.com/inward/record.url?scp=85072860939&partnerID=8YFLogxK
U2 - 10.1016/j.jtbi.2019.110026
DO - 10.1016/j.jtbi.2019.110026
M3 - Article
C2 - 31574283
AN - SCOPUS:85072860939
SN - 0022-5193
VL - 484
JO - Journal of Theoretical Biology
JF - Journal of Theoretical Biology
M1 - 110026
ER -