142 ALICK ISAACS 



D. Mechanism of Release of Virus and Virus Filaments 



During the multiplication of bacteriophages release of virus occurs when the 

 bacteria lyse. The results quoted in the previous three sections show that for 

 most animal viruses virus release can occur without cell lysis. Nevertheless, 

 there is a range of behavior from a virus such as western equine encephalitis 

 virus, which is very rapidly released from cells within a minute or two of its 

 maturation, to a virus like that of varicella in which release is minimal under 

 ordinary conditions of culture, and spread mostly occurs directly from one 

 cell to its neighbors. Further details of the mechanism of virus release are 

 best investigated by morphological studies; these are reviewed in Chapter 5. 

 In passing, however, it may be noted that there is some morphological evidence 

 to justify the biological findings on virus release for different viruses. Thus, 

 Lwoff et al. (1955) studied the appearance of single cells by phase-contrast 

 microscopy in parallel with biological observations on the release of polio- 

 myelitis virus. A hyaline zone appeared at the periphery of the cell just before 

 virus release occurred and underwent a pronounced vacuolization during the 

 time of release. This suggests that release of virus occurs through lysis of part 

 of the cell and that there was extensive cell disruption by the time virus 

 release ended. On the other hand, Robinow (1950) found that vaccinia virus 

 was excreted from cells along narrow filaments of cytoplasm protruding from 

 the cells. The virus appeared to pass to the tip of these stalks and then to 

 leave the cell with only minimal damage to the cell surface. There is a further 

 contrast in a virus like adenovirus, which Morgan et al. (1956a) demonstrated 

 in their beautiful electron micrographs to be almost exclusively intranuclear, 

 and in influenza virus particles, which could be found just beneath the cell 

 surface only (Morgan et al., 1956b). Presumably, influenza virus particles, in 

 contrast with adenoviruses, are finally assembled just beneath the cell 

 surface and are excreted from the cell soon after they are formed. 



From the biological point of view, one of the most interesting phenomena 

 bearing on the question of formation and release of virus particles is the 

 occurrence of filamentous forms of virus. Since they were first described by 

 Mosley and WyckofT (1946) filaments have been found associated with almost 

 all members of the myxovirus group, but they are most characteristic of 

 recently isolated strains of influenza virus A (Chu et al., 1949). The evidence 

 obtained by Donald and Isaacs (1945b) from particle counts and infectivity 

 titrations and on the effect of ultrasonic vibrations suggested that filaments 

 were infectious, and that they could be fragmented into many hemagglutina- 

 ting segments but without increasing the number of infective units. Burnet 

 (1956) found that filaments could be ruptured by suspending them in water 

 without reducing significantly the infectivity of the preparation; he suggested 

 that infectivity was limited to the sphere frequently found at the tip of the 

 filaments. Burnet also noted that filaments had some of the physicochemical 



