How Cells Tune Viral Mechanics-Insights from Biophysical Measurements of Influenza Virus

During replication, the physical state of a virus is controlled by assembly and disassembly processes, when particles are put together and dismantled by cellular cues, respectively. A fundamental question has been how a cell can assemble an infectious virus, and dismantle a virus entering an uninfected cell and thereby trigger a new round of infection. This apparent paradox might be explained by considering that infected and uninfected cells are functionally different, or that assembly and disassembly take place along different cellular pathways. A third possibility is that the physical properties of newly assembled viruses are different from the infection-ready viruses. Recent biophysical experiments measured the stiffness of single Influenza viruses and combined this with biochemical measurements and cell biological assays. Besides inducing the fusogenic state of hemagglutinin, low pH cues softened the virus and precluded aggregation of viral ribonucleoprotein particles with the matrix protein M1. The recent experiments suggest a two-step model for Influenza virus entry and uncoating involving low pH in early and late endosomes, respectively. I conclude with a short outlook into how combined biophysical and cell biological approaches might lead to the identification of new cellular cues controlling viral uncoating and infection.