Abstract
Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and substantial viral decline (about 2 to 4 logs within 1 day) after the peak can be explained by the killing of infected cells mediated by interferon activated cells, such as natural killer cells, during the innate immune response. After the viral load declines to a lower level, the loss of interferon-induced antiviral effect and an increased availability of target cells due to loss of the antiviral state can explain the observed short phase of viral plateau in which the viral level remains unchanged or even experiences a minor second peak in some animals. An adaptive immune response is needed in our model to explain the eventual viral clearance. This study provides a quantitative understanding of the biological factors that can explain the viral and interferon kinetics during a typical influenza virus infection.
Highlights
Despite vaccines and antiviral agents, influenza A virus infection remains a major public health problem worldwide
Commonly referred to as the flu, is a contagious respiratory illness caused by influenza virus infections
We address this question by developing mathematical models that include both innate and adaptive immune responses, and fitting them to experimental data from horses infected with equine influenza virus
Summary
Despite vaccines and antiviral agents, influenza A virus infection remains a major public health problem worldwide. The immune response to influenza virus infection plays an important role in controlling the virus within a host. An important cytokine produced during the innate immune response is type I interferon (mainly IFN-a/b). The secretion of IFN-a/b by infected epithelial cells is important for the initiation of the antigen-specific adaptive immune response [11,12], which in mice takes approximately 5 days to begin in the lung [13]. The adaptive immune response mainly consists of cytotoxic CD8+ T cells eliminating infected cells and antibodies neutralizing the virus [11]. It is important for clearing the virus and provides immunity against future influenza virus infections. Because of limited information about influenza pathogenesis and the host immune response in humans, various animal models, such as mice, ferrets, and horses [14,15,16,17], have been used to obtain a better understanding of the biological mechanisms underlying viral control
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