Defective-interfering (DI) RNAs of influenza viruses: origin, structure, expression, and interference.

Abstract

Influenza virus was the first virus for which defective-interfering particles were reported. Von Magnus (1947) observed that when he passaged influenza viruses serially undiluted in embryonated chicken eggs, both the amount of total virus particles as assayed by hemagglutinating units (HAU) and the amount of infectious virus particles as assayed by egg infectivity titer (EID50) decreased. However, he observed that the proportion of infectious particles as assayed by EID50 decreased precipitously when compared to the total virus particle (HAU) production. During the undiluted passages many particles were produced which were noninfectious. These noninfectious influenza virus particles produced at high multiplicity were called “incomplete” particles. Von Magnus (1951 a–c) also described the phenomenon of interference when he reported that these “incomplete” particles interfered with the multiplication of complete (infectious, nondefective, or standard) virus particles. This phenomenon of multiplicity dependent production of noninfectious virus particles is also called the “von Magnus phenomenon.” Since this observation was made with influenza viruses, similar multiplicity-dependent formation of noninfectious particles has been observed with almost all animal viruses carefully studied to date; indeed, formation of such particles has also been reported for plant, yeast, and bacterial viruses (Kane et al. 1979; Mills et al. 1967) and, thus, probably represents a general phenomenon for all viruses. The term “defective-interfering” (DI) particles was introduced by Huang and Baltimore (1970) to describe the definitive characteristics of these noninfectious particles and to separate them from other noninfectious particles which may be noninterfering.