14:3/ Structure of Viruses 251 



the size and shape of the plaque, the strains of bacteria it will infect, 

 induction time, pW sensitivity, heat sensitivity, and shape and size as 

 determined by the methods of Section 3.) This spontaneous change is 

 called a mutation. Once a mutation has occurred, descendants of the 

 mutant phage will reproduce the new characteristics faithfully. 



Thus, bacteriophages are similar to living organisms in that they 

 reproduce, exhibit genetic recombination, and also undergo mutations. 

 They differ from living cells in not metabolizing outside of bacterial 

 cells, in failing to show irritability outside of cells, and in the simplicity 

 and uniformity of the complete bacteriophage. Other viruses behave 

 similarly to bacteriophage in most respects. The largest ones such as 

 influenza virus particles show neither the simplicity nor the uniformity 

 of bacteriophages. However, the general pattern of initial attraction, 

 cellular entry, induction period, production of many replicas of the 

 original virus particle, and eventual cellular destruction is common to 

 all viruses. 



3. Virus Studies Using Physical Methods 



A number of different types of physical techniques have been used to 

 study the nature and activity of virus particles. Several of these methods 

 are discussed briefly in this section: specifically, electron microscopy, 

 ultracentrifugation, electrophoresis, and bombardment with ionizing 

 radiation. 



Electron microscopes are needed because virus particles are so very 

 small. A few of the largest viruses have maximum diameters of about 

 400 m/x. The smallest separation resolvable with a light microscope is 

 about one-half of this (see Chapter 23 for proof of resolution of the light 

 microscope). Therefore, the largest viruses are barely visible in the 

 light microscope. The phages and most viruses are much smaller, as is 

 indicated in Table I. They cannot be seen with light microscopes. 



Electron microscopes can resolve separations of 1 m^ (10 A) or slightly 

 less. Accordingly, suitable electron micrographs not only show the 

 existence of the viruses and phages as separate particles, but also allow 

 one to observe the shape and size of these particles. Rough particle 

 counts show that the particles seen with the electron microscope are the 

 same as those counted by plating techniques. The major disadvantage 

 of electron microscopy is that the samples must be dried. As the air- 

 water interface moves across the small particles, it may exert tremendous 

 forces tending to distort them. 



A novel way of avoiding this interface effect is to replace the water 

 with ethyl alcohol and then liquid C0 2 . This is then taken continuously 



