Comparative syncytia formation dynamics of coronavirus MHV-A59 and pneumovirus hRSV A2 and incorporation into improved kinetic virus replication models.

Abstract

Replication models have been developed to describe the replication dynamics of a variety of viruses to better understand the kinetics and key contributing factors affecting infectivity and spread. However, accurate representations of the dynamics of virus replication observed in vitro and in vivo are often limited due to the failure of these models to account for both environmental influences, such as temperature, and the variety of possible mechanisms employed by viruses to spread. Several major families of viruses including paramyxoviruses, pneumoviruses and coronaviruses, induce and use the formation of syncytia, large multinucleated cell masses formed through fusion of cells, to aid in spread to neighbouring susceptible cells. In this study, we evaluate and compare both the dynamics and roles of temperature and syncytia formation on the replication of two different fusogenic viruses in vitro: human respiratory syncytial virus (hRSV) and a murine coronavirus, mouse hepatitis virus (MHV). Thermal stability, replication kinetics and both the rates and dynamics of syncytia formation were evaluated for hRSV and MHV. These data were then incorporated into a novel and improved replication model for each of the two viruses, which provides new insights into the contributions of both temperature and syncytia formation in the replication of fusogenic viruses.