Virus Action and Replication 131 



Two kinds of viruses, both containing RNA, have been studied 

 most extensively in this way— myxoviruses (specifically influenza 

 and fowl plague virus) and small spherical viruses (poliovirus, 

 encephalomyocarditis virus and Western equine encephalitis virus) . 

 I shall describe briefly the sequence of events in the formation of 

 fowl plague virus and poliovirus. 



Fowl Plague Virus 



Work in Schafer's laboratory in Tubingen has established that 

 fowl plague virus consists of at least two proteins plus a lipid and 

 RNA (60). One protein, which is associated with the RNA in 

 the S antigen and which can be released from the whole virus 

 particle by ether treatment, still in association with the RNA, 

 first becomes detectable by fluorescent antibody staining in the 

 nucleus of cells three hours after infection. By four hours after 

 infection it is also found in the cytoplasm. The RNA which is 

 enclosed by this protein is also presumed to be formed in the 

 nucleus. The hemagglutinating antigen, on the other hand, is 

 formed in the cytoplasm. By the use of 5-fluorophenylalanine 

 (FPA) as an inhibitor of viral formation, the sequence of forma- 

 tion of proteins has been determined. Infected cells exposed to 

 FPA before one hour after infection form no viral antigens. Since 

 the virus apparently penetrates the cell, this may be an indication 

 that a new protein other than viral precursor protein must be 

 formed to allow the subsequent steps in virus production to occur. 

 If two hours elapse before treatment, S antigen appears to be 

 formed normally, but neither the hemagglutinating antigen nor 

 the infectious virus is foimed. By three hours after infection the 

 production of hemagglutinating activity and infectivity have begun 

 to escape inhibition and by six to seven hours after infection FPA 

 has no effect. The formation of infectious particles is, however, 

 more sensitive to FPA than the formation of hemagglutinating 

 antigen, an indication that these are separate processes (61). 



The virus particle thus has its origins in different parts of the 

 cell; then, by a transport process which also involves protein 

 synthesis, the whole particle is brought together at the cell surface 

 and completed. Nothing more is known about events within the 

 first hour of infection which are necessary for the initiation of 

 replication of viral precursor molecules. 



