Cyclic Production of Vesicular Stomatitis Virus Caused by Defective Interfering Particles

Abstract

Purified standard and defective interfering (DI) particles of vesicular stomatitis virus (VSV) were reconstituted, and the mixture was continuously passaged for six 24-hr growth periods in Chinese hamster ovary cells in suspension cultures. The cultures were monitored for cellular viability, for intracellular virus-specific RNA, for total extracellular viral particles, and for production of plaque-forming standard VSV. During the six passages, there was a cyclic, overlapping pattern of synthesis of both DI and standard VSV particles; decline in the production of standard virus was always preceded by large amounts of DI particles. Intracellular virus-specific RNA synthesis reflected the pattern of production of extracellular particles. Viral antigens represented by nucleocapsids accumulated in cells when DI particles were being produced in large quantities. These nucleocapsids contained RNA of DI particles. Under other conditions, infected cells were able to survive longer than usual and were resistant to superinfection by standard VSV. Preliminary evidence indicates that this resistance was due to surface interference. Therefore, a wide variety of different interactions between virus and host occurs simply by varying the total concentration of viral particles and the relative concentrations of standard and OI particles in these preparations.