268 1. lODOACETATE AND lODOACETAMIDE 



yet known of the groups involved or the nature of the primary interference 

 in the complex sequence of virus multiplication. 



Some work has been done on the application of these inhibitors to host- 

 virus preparations. The number of lesions in detached leaves produced by 

 tobacco mosaic virus is reduced slightly by 0.05 mM iodoacetate and quite 

 markedly by 0.3 mM (Chiba et al., 1953). Since azide and 2,4-dinitrophenol 

 do not reduce the lesion density, one suspects that mere reduction in ATP 

 cannot explain the effect of iodoacetate. Iodoacetate does not inhibit in 

 the dark, and may increase the number of lesions, so that an effect on photo- 

 synthesis is a possibility. The proliferation of vaccinia virus in chick em- 

 bryonic tissue over 4 days is markedly depressed by 0.054 roM iodoacetate 

 (R.L. Thompson, 1947). The yield of foot-and-mouth disease virus from 

 cultures of kidney cells is reduced 10% by 0.01 mM and 33% by 0.1 mM 

 iodoacetate, although there is no delay in the appearance of the virus (Po- 

 latnick and Bachrach, 1960). The effects are not counteracted by pyruvate, 

 so the site of attack may not be the EM pathway, although it could also 

 mean that virus multiplication is in some way dependent directly on gly- 

 colysis. 



Turning now to bacteriophages, we shall examine first the results which 

 have been obtained on coliphages. Spizizen (1943) allowed the phage to 

 adsorb onto the bacterial cells, washed the cells, and then placed them in 

 nutrient media which allowed phage production. Iodoacetate at 0.5 mM 

 completely abolished phage multiplication whatever the medium used. Al- 

 though inhibition of phage multiplication has been generally observed, it 

 seems clear that iodoacetate is not selective and that bacterial growth is 

 simultaneously depressed (Ryzhkov and Semich, 1947; Czekalowski, 1952; 

 Dolby, 1955). Low concentrations of iodoacetate (0.05 mM) block phage 

 proliferation and reduce bacterial growth, whereas higher concentrations 

 (0.25-1.35 mM) destroy both phage and bacteria. There may be a greater 

 effect on phage, however, as indicated in the study of Dolby, in which the 

 inhibition index for T2 coliphage is 0.03 at 0.05 mM iodoacetate and for 

 the bacteria is 0.77, this pointing to a differential, if not a selective, effect. 

 Baer et al. (1955) found that the addition of 1 mM iodoacetate to three 

 host-virus systems, including coliphage, at various times during the proli- 

 feration of phage leads to immediate and complete inhibition of further 

 phage formation, so that the final phage yields correspond to the amount 

 present when the inhibitor is added; they suggested that iodoacetate could 

 be used to titrate mature intracellular phage at any time. There is no effect 

 on free phage or on its attachment or penetration into the bacteria. 



The development of other phages is well inhibited by iodoacetate. If 

 staphylococci containing "phage precursor" are treated with 0.1 mM iodo- 

 acetate for over 15 min, there is a marked reduction of the phage yield 

 (Krueger and Scribner, 1940). Phage precursor can be inactivated without 



