194 1. MALONATE 



and similar results were reported for psittacosis virus (Morgan, 1954). In 

 neither case does malonate depress the growth of the tissue cultures, noi 

 does it inhibit the cellular contractions of chick heart cultures. Very slight 

 effects of malonate at concentrations from 10 to 100 mM were observed 

 with foot-and-mouth disease virus in bovine kidney culture cells (Polatnick 

 and Bachrach, 1960). Since there is little inhibition of the respiration, it is 

 possible that malonate does not penetrate adequately. At 100 mM, respira- 

 tion is inhibited 23%, virus yield perhaps 20%, and there is a 10 min delay 

 in the appearance of virus. Finally, malonate was found to actually stimu- 

 late feline pneumonitis virus proliferation in the isolated chick embryo yolk 

 sac, 10 mM increasing the virus titer about 33% (Moulder et al., 1953). 

 Thus a wide variety of effects have been observed with different viruses 

 and host cells, no general conclusions being possible at this time. I am not 

 aware of any studies on the effects of malonate on the course of virus in- 

 fections in whole animals. 



Plant viruses have been inadequately investigated and results on the 

 tobacco mosaic virus only are available. Although malonate at 0.5 mM de- 

 creases the number of lesions/cm^ in detached tobacco leaves from 28.9 

 to 21.9, Chiba et al. (1953) felt that this result is statistically insignificant. 

 Ryzhkov and Marchenko (1954, 1955) reported that malonate inhibits 

 multiplication of this virus and that this is reversed by fumarate, but 

 Schlegel (1957) found only variable effects of 3 mM malonate on the yield 

 of virus in leaf discs. The spraying of 10 mM malonic acid solutions (pH 

 2.7-3.6) onto the leaves of bean plants decreases the number of virus lesions 

 68% without leaf damage (Matthews and Proctor, 1956), but this may be 

 unrelated to the action of malonate on the cycle inasmuch as succinic acid 

 is even more inhibitory. This is probably a nonspecific acid effect because 

 the cycle intermediates usually increase the virus yield when they are added 

 to leaf cultures. 



It is somewhat surprising that malonate has no demonstrable effect on 

 the multiplication of E. coli phage. Spizizen (1943) found no effect at 10 mM 

 under any conditions of virus growth, and Czekalowski (1952) reported no 

 actions on either T2 phage or host cells at concentrations from 0.1 to 100 mM. 

 It may well be that phage proliferation is not directly dependent on the 

 energy derived from the cycle, but inhibition by 2,4-dinitrophenol, cyanide, 

 and fluoride is observed. In fact, Czekalowski stated that all the inhibitors 

 that depress phage selectively seem to act in some manner on the cyto- 

 chrome system and are able to inhibit succinate oxidase; yet the most 

 specific inhibitor for this enzyme is inactive. Lack of penetration is an 

 unlikely explanation and this failure of malonate to inhibit deserves further 

 study. 



