Quantifying the effect of trypsin and elastase on in vitro SARS-CoV infections

Abstract

The SARS coronavirus (SARS-CoV) has the potential to cause serious disease that can spread rapidly around the world. Much of our understanding of SARS-CoV pathogenesis comes from in vitro experiments. Unfortunately, in vitro experiments cannot replicate all the complexity of the in vivo infection. For example, proteases in the respiratory tract cleave the SARS-CoV surface protein to facilitate viral entry, but these proteases are not present in vitro. Unfortunately, proteases might also have an effect on other parts of the replication cycle. Here, we use mathematical modeling to estimate parameters characterizing viral replication for SARS-CoV in the presence of trypsin or elastase, and in the absence of either. In addition to increasing the infection rate, the addition of trypsin and elastase causes lengthening of the eclipse phase duration and the infectious cell lifespan.

Keywords: Coronavirus; In vitro infections; Mathematical model; Parameter estimation; Protease.

Fig. 1

Schematic of the mathematical model. Target cells are infected by virus at rate β. They remain in the eclipse phase for a time τ_E and actively release virus at rate p for a time τ_I.

Fig. 2

Fits for SARS-CoV data in the presence of trypsin (left) or elastase (center), and in the absence of either (right).

Fig. 3

Parameter distributions for SARS-CoV infecting VeroE6 cells in the presence of elastase, trypsin or absence of both. Parameters are: infection rate (top left), viral production rate (top right), eclipse phase duration (center left), infectious cell life span (center right), and infecting time (bottom).