  The role of direct cell-to-cell spread in viral infections - where virions
spread between host and susceptible cells without needing to be secreted into
the extracellular environment - has come to be understood as essential to the
dynamics of medically significant viruses like hepatitis C and influenza.
Recent work in both the experimental and mathematical modelling literature has
attempted to quantify the prevalence of cell-to-cell infection compared to the
conventional free virus route using a variety of methods and experimental data.
However, estimates are subject to significant uncertainty and moreover rely on
data collected by inhibiting one mode of infection by either chemical or
physical factors. These methods assume that this inhibition process fully
eliminates its target mode of infection while exactly preserving the dynamics
of the other. In this work, we provide a framework for estimating the
prevalence of cell-to-cell infection from data which is experimentally
obtainable without the need for additional interventions, and two standard
mathematical models for viral dynamics with the two modes of infection. We
provide guidance for the design of relevant experiments and mathematical tools
for accurately inferring the prevalence of cell-to-cell infection.

Quantitative Methods;Tissues and Organs