Initial Phase of Replication of Plus-Stranded RNA Viruses

The author presents theoretical mean-field analysis of the initial phase of the kinetics of intracellular replication of plus-stranded RNA viruses, which are abundant and include, e.g., the hepatitis C virus (HCV). The treatment is based on the conventional concept that the replication process of such viruses takes place at the membrane complexes formed with participation of viral proteins, e.g., NS5A in the HCV case. The key novel prediction supported by Monte Carlo calculations is that this scheme may be insufficient in order to describe the very initial phase of the process, because the initial intracellular viral RNA and protein populations may in this case go extinct rather than overcome the kinetic barrier for transition to the full-scale infection of a host cell. Practically, this means that in such situations, the conventional replication scenario should be complemented by another pathway, e.g., by replication outside the membrane without viral proteins, which operates in the very beginning.