Repulsion of Superinfecting Virions: A Mechanism for Rapid Virus Spread

Viruses are thought to spread across susceptible cells through an iterative process of infection, replication, and release, so that the rate of spread is limited by replication kinetics. Here, we show that vaccinia virus spreads across one cell every 75 minutes, fourfold faster than its replication cycle would permit. To explain this phenomenon, we found that newly infected cells express two surface proteins that mark cells as infected and, via exploitation of cellular machinery, induce the repulsion of superinfecting virions away toward uninfected cells. Mechanistically, early expression of proteins A33 and A36 was critical for virion repulsion and rapid spread, and cells expressing these proteins repelled exogenous virions rapidly. Additional spreading mechanisms may exist for other viruses that also spread faster than predicted by replication kinetics.