INHIBITION OF RELEASE OF VACCINIA VIRUS BY N1-ISONICOTINOYL-N2-3-METHYL-4-CHLOROBENZOYLHYDRAZINE

Abstract

N1-isonicotinoyl-N2-3-methyl-4-chlorobenzoylhydrazine (IMCBH) is a selective inhibitor of vaccinia virus multiplication. In concentrations up to 50 µg/ml, IMCBH causes neither toxic morphologic changes, nor does it inhibit the multiplication of cells. Viruses other than vaccinia are not affected by IMCBH. The virus-inhibitory effect of IMCBH is dependent on the type of host cell used, i.e., the compound is effective in chick embryo fibroblasts and monkey kidney cells but not in L cells. IMCBH does not exhibit any protecting effect on vaccinia virus-infected mice or rabbits. IMCBH interferes with virus release: in single cycle experiments in chick embryo fibroblasts, IMCBH strongly blocks the release of vaccinia virus at concentrations as low as 3 µg/ml, while intracellular virus synthesis is hardly affected. Viral cytopathic changes are completely suppressed by IMCBH within the span of a single cycle infection, although extensive changes eventually occur. By inhibiting virus release from initially infected cells, IMCBH markedly inhibits the multiplication of vaccinia virus in cell cultures infected at low virus/ cell multiplicities. IMCBH does not inhibit the early toxic cytopathic changes induced by large inocula of vaccinia virus in BHK21 cells.