201 F. L. HORSFALL, JR. 



inhibits multiplication in the next cycle, as would be expected from its 

 activity during the latent period. 



The substance does not inactivate the infectivity of the virus particle 

 (Horsfall and McCarty, 1947b) and does not prevent adsorption of the virus 

 by erythrocytes or lung tissue (Horsfall and McCarty, 1947a). Oxidation with 

 periodic acid, sufficient to destroy specific serological activity, does not 

 diminish the inhibitory activity of the polysaccharide (Horsfall and McCarty, 

 1947a) but does markedly diminish the toxic effects of the substance in the 

 mouse lung (Ginsberg and Horsfall, 1951b). Although depolymerization has 

 no effect on inhibitory activity, the aldobionic acid derived from the poly- 

 saccharide by acid hydrolysis is inactive (Horsfall and McCarty, 1947a). 



All attempts to discover the biochemical basis for the inhibitory activity of 

 K. pneumoniae, type B, capsular polysaccharide have been unsuccessful. The 

 precise chemical structure of the substance has not been established. There 

 are, however, good indications that its effect on host cells may be specific in 

 character and dependent on a selective biochemical alteration. Although the 

 polysaccharide is highly active as an inhibitor of multiplication of pneumonia 

 virus of mice in the mouse lung (as little as 2 /xg. given once causes 90 % 

 inhibition), it has no effect on the multiplication of influenza viruses in the 

 lung of the same host species (Horsfall and McCarty, 1947a; Ginsberg et al., 

 1948). Moreover, although some other polysaccharides, including the capsular 

 substances from K. pneumoniae, types A and C, and streptococcus MG, as 

 well as blood group A substance and dextran, synthesized from sucrose in 

 vitro by a cell-free enzyme, have similar inhibitory activity on the multiplica- 

 tion of PVM, numerous other polysaccharides do not (Horsfall, 1952). Among 

 the latter is the capsular polysaccharide of pneumococcus, type 2, which, 

 although related serologically to that of K. pneumoniae, type B, is wholly 

 inactive as an inhibitor (Ginsberg et al., 1948). 



It is curious that the polysaccharide is effective as an inhibitor only when it 

 is given intranasally in mice (Horsfall and McCarty, 1947a). This is also the 

 only route of inoculation that leads to infection with PVM (Horsfall and Hahn, 

 1940). No adequate explanation for the decisive character of the route of 

 administration has been offered, but it may be that the large size of the 

 polysaccharide molecule prevents its diffusion into the lung in adequate 

 concentration to yield inhibition when given by other routes. In support of 

 this suggestion, it is known that the substance is poorly and irregularly 

 transported from the yolk sac to the allantoic fluid in the chick embryo 

 (Ginsberg et al., 1948). 



In addition to its inhibitory effect on the intracellular multiplication of 

 PVM, K. pneumoniae, type B, capsular polysaccharide is a potent inhibitor 

 of mumps virus multiplication in the allantoic sac of the chick embryo 

 (Ginsberg et al., 1948). Although there are some data indicating that the 



