A within-host mathematical model of H9N2 avian influenza infection and type-I interferon response pathways in chickens. (21st August 2020)

• Record Type: Journal Article
• Authors: Xie, Xiao-Ting; Yitbarek, Alexander; Uddin Khan, Salah; Sharif, Shayan; Poljak, Zvonimir; Greer, Amy L
• Is Part Of: Journal of theoretical biology. Volume 499(2020)
• Publication Date: 2020-08-21
• Subjects: Avian influenza -- Mathematical model -- Virus dynamics -- Cellular immunity -- Domestic chickens; Biology -- Periodicals; Biological Science Disciplines -- Periodicals; Biology -- Periodicals; Biologie -- Périodiques; Theoretische biologie; Biology; Periodicals; 571.05
• DOI: 10.1016/j.jtbi.2020.110320
• Languages: English
• ISSNs: 0022-5193

Abstract

Highlights: Three major type-I interferon (IFN) pathways are known to reduce virus shedding from avian influenza infected chickens. A within-host mathematical model was used to assess the effect of these IFN pathways on cloacal virus shedding. The effect of a cellular latent period was also examined in the model. Inclusion of type-I IFN pathways are necessary for replicating the experimental cloacal virus shedding data. Inclusion of a latent period generally allows for improved model fit to the experimental data. Abstract: Chickens infected with avian influenza virus (AIV) transmit the virus via respiratory and cloacal shedding. While previous mathematical models have shown that the innate immune response is necessary for the early suppression of virus production in infected respiratory cells, the different pathways by which the innate immune response can affect cloacal viral shedding have not been studied in chickens. The present study aims to evaluate the sensitivity of H9N2 low pathogenic AIV shedding in chicken gastrointestinal cells to different type-I interferon (IFN) response pathways, and to determine the impact of a cellular eclipse phase (latent period) on the time to peak virus shedding using a mathematical model describing within host viral kinetics. Our model results demonstrate that a mechanistic model that incorporates 1) the intracellular antiviral effects of type-I IFN on virus production, 2) destruction of infected cells by type-I IFN activated Natural Killer cells, and 3) an eclipse phase is most consistent with experimental cloacal virus shedding data. These results provide a potential mechanistic explanation for the delay to peak cloacal virus shedding observed in experimental studies conducted in chickens, as well as an improved understanding of the primary type-I IFN pathways involved in the control of cloacal virus shedding, which may lead to the development of more targeted vaccine candidates.