Speaker
Description
Influenza viruses remain a global health concern; thus, we examine the interplay of host-pathogen interaction using math models. Using human challenge data (Hayden 1999, 2000), we fit our model to analyze the heterogeneity of the observations. We tested hypotheses of immune factors influencing viral kinetics and distinguished the immune components between those who cleared and those who experienced prolonged viral shedding. Key findings revealed different immunological signatures of individuals that exhibited rapid expansion of immune effector cells and facilitating a quicker viral clearance than high shedders with delayed adaptive immune responses, correlating to their prolonged infection.
Further, we incorporated treatment effects into our viral dynamics model to analyze the mechanisms of action of Oseltamivir (Tamiflu®) and Baloxavir (Xofluza®). Simulations explained the qualitative differences of virus kinetics when treated with Oseltamivir, a neuraminidase inhibitor, versus Baloxavir, a cap-dependent endonuclease inhibitor. Oseltamivir prevents the release of newly formed virions from infected host cells. In contrast, Baloxavir, blocks viral mRNA transcription early in replication. Our results explained that alleviation of infection symptoms occurs more rapidly when treated with Baloxavir as the antiviral stops new viral production early leading to a rapid reduction, whereas Oseltamivir resulted in gradual decline of viral load reducing the spread of virus to new cells.
Bibliography
Hayden, F. G., Treanor, J. J., Fritz, R. S., Lobo, M., Betts, R. F., Miller, M., Kinnersley, N., Mills, R. G., Ward, P., & Straus, S. E. (1999). Use of the Oral Neuraminidase Inhibitor Oseltamivir in Experimental Human Influenza: Randomized Controlled Trials for Prevention and Treatment. JAMA, 282(13), 1240–1246. https://doi.org/10.1001/jama.282.13.1240
Hayden, F. G., Jennings, L., Robson, R., Schiff, G., Jackson, H., Rana, B., McClelland, G., Ipe, D., Roberts, N., & Ward, P. (2000). Oral Oseltamivir in Human Experimental Influenza B Infection. Antiviral Therapy, 5(3), 205–213. https://doi.org/10.1177/135965350000500305
