Kinetic Modeling of Virus Growth in Cells

Abstract

When a virus infects a host cell, it hijacks the biosynthetic capacity of the cell to produce virus progeny, a process that may take less than an hour or more than a week. The overall time required for a virus to reproduce depends collectively on the rates of multiple steps in the infection process, including initial binding of the virus particle to the surface of the cell, virus internalization and release of the viral genome within the cell, decoding of the genome to make viral proteins, replication of the genome, assembly of progeny virus particles, and release of these particles into the extracellular environment. For a large number of virus types, much has been learned about the molecular mechanisms and rates of the various steps. However, in only relatively few cases during the last 50 years has an attempt been made-using mathematical modeling-to account for how the different steps contribute to the overall timing and productivity of the infection cycle in a cell. Here we review the initial case studies, which include studies of the one-step growth behavior of viruses that infect bacteria (Qβ, T7, and M13), human immunodeficiency virus, influenza A virus, poliovirus, vesicular stomatitis virus, baculovirus, hepatitis B and C viruses, and herpes simplex virus. Further, we consider how such models enable one to explore how cellular resources are utilized and how antiviral strategies might be designed to resist escape. Finally, we highlight challenges and opportunities at the frontiers of cell-level modeling of virus infections.

Biophysical modeling of the SARS-CoV-2 viral cycle reveals ideal antiviral targets

“…1; reviewed in (9,10)). Mass action and chemical rate equations were used to mathematically describe the system using an approach similar to that taken previously to model the life cycle of other viral systems (reviewed in (11); see Materials and Methods), and the resulting series of ordinary differential equations solved numerically. As an initial condition we assumed that a single virion was bound to the surface of an individual cell, which was then internalized to initiate the replication cycle.…”

Transcript degradation and codon usage regulate gene expression in a lytic phage

“…For a recent review of this type of modeling, see Ref. [16]. Kinetic models can capture complex gene regulatory behavior and exhibit rich dynamics, but ultimately they are too simplistic to accurately describe gene expression.…”

“…One of the most widely studied bacteriophages is bacteriophage T7, whose genome was first sequenced in 1983 [10]. A wealth of specific knowledge about T7's genes, gene regulation, and gene interactions has been accumulated since [11], and this knowledge has enabled the development of detailed mechanistic models of the viral life cycle inside a bacterial cell [12][13][14][15][16].…”

Life cycle process dependencies of positive-sense RNA viruses suggest strategies for inhibiting productive cellular infection

“…Quantitative measurements and mathematical modeling has tremendously enhanced our understanding of how the subtleties of intracellular processes shape the outcome during viral infections [16,17,18,19,20,21,22,23,24] (reviewed in [25]). Understanding derived from these (and combined with their extensions that incorporate extracellular and immune response) have been used to determine effectiveness of interventions and combinations thereof [26,27,28,29,30].…”