INHIBITION OF MULTIPLICATION 203 



(1) Klebsiella pneumoniae, type B, (Friedlander bacillus) capsular polysac- 

 charide (Fr. B), which inhibits pneumonia virus of mice (PVM) reproduction 

 (Ginsberg and Horsfall, 1951b); (2) 2, 5-dimethylbenzimidazole (MB), which 

 inhibits influenza B virus multiplication (Tamm et al., 1953a; Tamm and 

 Tyrrell, 1954); (3) DL-methoxinine, which inhibits influenza A virus multi- 

 plication (Ackermann and Maassab, 1954b); (4) 5, 6-dichloro-l-/3-D-ribo- 

 furanosylbenzimidazole (DRB), which inhibits influenza B virus multiplica- 

 tion (Tamm and Tyrrell, 1954) and poliovirus, type 2, multiplication (Tamm, 

 and Nemes, 1957); (5) jo-fluorophenylalanine (FPA), which inhibits poliovirus, 

 type 3, multiplication (Ackermann et ah, 1954); (6) levo-y-(o-chlorobenzyl)-S- 

 oxo-y-phenyl caproic acid (caprochlorone), which inhibits influenza A virus 

 multiplication (Liu et al., 1957a); (7) 5, 6-dichloro-l-a-D-arabinopyranosyl- 

 benzimidazole (DAB) which inhibits poliovirus, type 2, multiplication 

 (Tamm and Nemes, 1957). 



To prove that a substance inhibits during the latent period, it is essential 

 to use single-cycle multiplication experiments, comparable to the one-step 

 growth experiment devised for bacteriophage (Ellis and Delbriick, 1939), and 

 to add the inhibitory substance at various intervals after attachment and 

 penetration of the virus. Perhaps because of the technical difficulties and 

 large number of measurements that are required, such kinetic experiments 

 have not been frequently carried out. The small number of substances known 

 to cause inhibition during the latent period is probably attributable more to 

 lack of adequate data than to special features of the substances that are known 

 to be inhibitory during this interval. 



1. Klebsiella Pneumoniae, Type B, Capsular Polysaccharide (Fr. B) 



This substance inhibits the multiplication of pneumonia virus of mice (PVM) 

 in the lung of the living mouse (Horsfall and McCarty, 1947a). In single-cycle 

 multiplication experiments (Ginsberg and Horsfall, 1951b), 0.1 mg. per mouse, 

 intranasally, markedly inhibited reproduction of the virus when given at 4, 8, 

 or 10 hours, but not at 12 hours after inoculation. Because the latent period of 

 PVM in the mouse lung is about 15 hours (Ginsberg and Horsfall, 1951a), it 

 appears that the polysaccharide is effective as an inhibitor only during the 

 first two-thirds of the interval. It seems clear on the basis of the time 

 relationships that it does not act by preventing attachment of the virus or 

 penetration of susceptible cells. Moreover, because it is ineffective during the 

 last third of the latent period, it is apparent that it does not affect either the 

 maturation of new infective virus particles or their eventual release from the 

 virus-infected cell (Horsfall, 1952). 



If the polysaccharide is given after the end of the latent period, e.g., at 18 

 hours, it has no effect on the yield of virus from the first cycle but effectively 



