Biomedical subjects
Publications and source records attributed to S J Mims.
Scanning electron microscopy of AKR cells chronically infected with AKR mouse leukaemia virus revealed that the number of budding virions was greatly increased in interferon-treated cells. These results, together with previous biochemical findings, suggest that in this system, interferon inhibits a late stage of virus assembly or release.
Rifamycin derivatives differing in the substitutent at the 4 position of the piperazinyliminomethyl side chain were tested for anti-poxviral activity. The effects of each derivative on wild-type vaccinia virus and on a mutant selected for resistance to rifampin were determined. Antiviral activity was measured in tissue culture by plaque inhibition, reduction in virus yield, and specific interruption of virus morphogenesis. Rifamycin derivatives containing H, ethyl, or propyl groups at the 4 position of the piperazinyliminomethyl side chain were much less active than rifampin, which has a methyl group at this position. Thus, minimal shortening or lengthening of the methyl piperazinyliminomethyl side chain of rifampin led to loss of specific antiviral activity. In contrast, the derivative containing an amino group at the 4 position of the piperazinyliminomethyl side chain had enhanced anti-poxviral activity.
Assembly of vaccinia virus envelopes and immature vaccinia particles was interrupted in HeLa cells treated with rifampin (rifampicin). The primary action of rifampin on vaccinia morphogenesis appeared to occur during the stage of envelope formation. When envelopes and immature particles were already present, maturation could continue, even in the presence of rifampin. It was demonstrated that the trilaminar membranes of irregular contour which accumulate in the presence of rifampin are precursors of virus envelopes. When rifampin was removed under controlled conditions, synchronous transitions were observed as the precursor membranes rapidly converted into uniformly curved envelope units with a 10- to 12-nm coat on the convex surface. These experiments provided an opportunity to examine the sequence of some early events in vaccinia morphogenesis. Initially, nascent envelopes remained in clusters around dense viroplasm. Large numbers of single immature particles appeared within 10 min. Nucleation of immature particles was the first evidence of core differentiation and began within 5 to 10 min. Development of lateral bodies and modeling of the biconcave cores was observed within 30 min, and structurally mature virions were present by 2 hr after the removal of rifampin. High resolution autoradiography showed that viral deoxyribonucleic acid, which labeled with (3)H-thymidine during rifampin treatment, was incorporated by the mature vaccinia which formed after rifampin was removed. Concentration of the viral deoxyribonucleic acid in core material evidently occurred after envelope assembly, probably coincident with nucleoid formation. Cytoplasmic crystalloid bodies accumulated during rifampin treatment; they appeared morphologically identical to vaccinia nucleoids and were heavily labeled by (3)H-thymidine.