I propose to analyze the structural polypeptides of the known human papovaviruses for possible genetic relatedness to SV40. The viruses include: DAR (PML-2) a variant of SV40 isolatd from the brain of a patient with progressive multifocal leukoencephalopathy (PML); JC, a distinct new papovavirus isolated from PML brain; BK, isolated from urine of a patient who had undergone renal transplantation; and human papilloma, which can be isolated from human warts. These viruses and SV40 will be labeled isotopically in vivo and purified, or purified virus will be labeled in vitro. The viral proteins will be analyzed on SDS polyacrylamide gels for molecular weight determinations, ureacetic acid gels for comparison with cell histones, and by isoelectric focusing for a more sensitive comparison. Since there is a selective incorporation of histones, we will analyze which histones are present in virions of each strain and the relative proportions of each, whether the host cell influences the histone composition of the virus, and whether virion histones are modified. Structural polypeptides of the various strains will be be purified by gel filtration in 6 M guanidine and ion exchange chromatography, and amino acid compositions and amino and carboxyl-terminal amino acid sequences determined. Comparative peptide analysis of tryptic digests of each polypeptide by two-dimensional thin layer chromatography and electrophoresis and by ion-exchange chromatography will be employed to identify regions of amino-acid sequence identity between capsid proteins of the various strains. The location of the structural polypeptides in the virion of each strain will be analyzed by enzymatic digestion, detergent treatments, chemical probes with protein reactive reagents, and generation of subviral particles. These studies will provide a sensitive analysis of the relatedness of the human papovaviruses to SV40.