Influenza virus population dynamics in the respiratory tract of experimentally infected mice

Abstract

Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.

Influenza Virus Infection Model With Density Dependence Supports Biphasic Viral Decay

“…Our data showed that viral loads are maintained at a high level between 2 d and 7 d pi (Figure 1). Sustained viral loads have been observed in several studies [6,10,21,24,38,46,51]. In some data sets, the peak appears more pronounced and is often followed by the plateau phase or a second, lower peak [1,4,6,10,17,21,24].…”

Influenza A virus infection kinetics: quantitative data and models

“…While the dynamics of influenza A virus have been investigated in various studies, the dynamics of influenza B virus, 103 which is also an important public health threat, have not been analyzed using kinetic models. The models developed thus far also generally do not incorporate multiple compartments, such as the lung, trachea, and nasopharynx, 61 that may have interesting dynamical differences. Integrating the extracellular events (e.g., virus production and infected cell death) with the intracellular kinetics (e.g., RNA replication and virus assembly) 23 or the transmission between hosts 104,105 may give insight into the various aspects of influenza pathogenicity including why some strains cause more inflammation or are more easily transmitted.…”

Two T‐Cell Populations Mediate Delayed‐Type Hypersensitivity to Murine Influenza Virus Infection

“…The flrst is that even freshly harvested virus preparations contain an excess of non-infectious virions, and these may persist in the mouse because permissive replication does not take place in the spleen [15] or footpad [this paper]. Even after the initial rapid replication of influenza virus in the lungs, the virus titre levels off [5,18], and this may reflect an accumulation of non-infectious virions. Thus, the mouse would be sensitized to produce both classes of DTH effector cells when infectious influenza virus preparations were injected.…”