Early events in the eclipse phase of influenza and parainfluenza virus infection

Within-host infectious disease models accommodating cellular coinfection, with an application to influenza

“…To date, very few studies have attempted to empirically quantify these relationships, making the appropriate choice of model structure difficult to decide upon. For influenza, the studies that do exist have shown that the timing and amounts of viral yield depend critically on cellular input, and that cumulative viral yield generally increases with cellular input [12,13]. Intriguingly, these results stand in contrast to the current structure of the model that we have presented.…”

“…While these within-host models capture many of the important features of within-host viral processes, the majority of them implicitly assume that cellular coinfection does not occur [9] or that cellular coinfection, if it occurs, does not affect the phenotypes of infected cells [10,11]. Yet several experimental findings point towards cellular multiplicity of infection having the potential to impact cellular phenotypes such as the rate at which infected cells produce viral output [12,13] and the probability of initiating an interferon response [14]. The implicit assumption that a cell’s multiplicity of infection does not impact its phenotypes is hard-wired into ‘microparasite’-structured models because these models generally only consider a single class of infected cells, regardless of cellular multiplicity of infection.…”

Coinfection of semi-infectious particles can contribute substantially to influenza infection dynamics

“…This implies that, although the viral load predictions from the TS model look similar to those of previous models [12], the infection mechanisms and the parameters obtained from fitting the TS model to data are different from what is suggested by previous models. The distinction between infection mechanisms is important when connecting experimental measurements and mathematical models, especially since the virion production rate of a cell may depend on the number of virions that have entered it [26,27]. Thus, our results indicate that experimentally determining the relationship between the viral input (i.e.…”

“…We expect that the viral output from doubly infected cells is higher than that from singly infected cells, i.e. p2 > p1 [26,27]. Of all virions produced, a constant fraction [9], f, of them are semi-infectious, while the remaining fraction are fully infectious.…”

Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility

“…This disparity results in a divergence in the effective MOIs of the individual gene segments. Because the kinetics of IAV gene expression increase with MOI, this divergence should generate a gene-dosage effect that reduces NA expression relative to other gene products (28). To test this notion, we generated a stock of PR8 lacking the NA vRNA segment (PR8 NoNA ) using reverse genetics.…”