Studies on the structure of infectious and non-infectious influenza virus
Non-infectious forms of influenza virus can be obtained in the laboratory under a variety of conditions and from various sources. They have been shown to differ in a number of biological and chemical properties from fully infectious particles. In the present study an attempt was made to differentiate between incomplete and infectious virus units on the basis of their appearance in the electron microscope. The PR 8 strain of influenza A was used throughout this investigation. Virus pellets were obtained on centrifugation of various materials which had been subjected to extensive purification and concentration procedures. These pellets were embedded in methacrylate and ultrathin sections were prepared for microscopic study. The examination of sections of infectious elementary bodies derived from standard seeds reveals a majority of particles with marked electron-dense centers which are surrounded by two well-defined concentrically arranged limiting layers. The latter are separated by a zone of lesser density. A second component which exhibits centers of low electron density can also be discerned although it appears to be present in minor proportion only. However, incomplete virus obtained on serial undiluted passage of allantoic fluid or in single egg passage of mildly heat-inactivated standard seed, as well as in HeLa cells, represents a heterogeneous aggregation of particles which differ considerably in shape and size. While their outer coats resemble those of the fully infectious units, little or no internal structural detail can be observed in most of them and the overall impression is that of hollow virus bodies. These differences are not seen when the infectivity of the virus is largely destroyed by prolonged exposure to 37°C in vitro. Sections of such particles cannot be distinguished from the originally infectious units. This lends further support to the hypothesis that incomplete virus arises by an altered replicating process rather than as the result of rapid inactivation in vivo.