Abstract
Coinfections with more than one respiratory virus can enhance or inhibit virus growth kinetics and disease severity depending on the underlying mechanism of interaction. Although some mechanisms are known (e.g., enhanced virus entry), viral-viral coinfections are only beginning to be examined in the laboratory and clinic. Thus, to understand how different mechanisms of viral interactions can affect viral titer kinetics, we developed and analyzed a mathematical model. Here, we focused on how coinfection leading to increases or decreases in viral infection rate, viral production rate, viral clearance rate, and infected cell death rate alters viral kinetics. While each of these types of interactions can lead to increases or decreases in total virus produced, each interaction type alters the viral kinetics in characteristic ways. We found that decreasing the viral clearance rate leads to the largest increase in total virus produced relative to coinfection without direct interactions. We varied the strength of interactions and timing of viral infections to determine how these critical factors impact results. Our results suggest that the mechanisms underlying virus-virus interactions and the relative timing of infection of the two viruses impact the rate of viral titer increase, the timing of peak, and the rate of viral titer decrease after peak, and thus the total duration and severity of disease.