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Purification and characterization of a strain of coxsackievirus b4 of human origin that induces diabetes in mice

A diabetogenic strain of coxsackievirus B4 of human origin has been purified to study its biochemistry and diabetogenicity. Tissue culture cells infected with the virus contain two distinct types of particles—virions and membrane‐bound virions (MBV). MBVs are lighter (ρ = 1.29) than virions (ρ = 1.34), and they contain relatively more protein than RNA. Virions contain four capsid proteins, VP1–4, of various molecular weights: VP1, 37,500; VP2, 36,000; VP3, 26,000; and VP4, 5,500. MBVs contain three of these proteins and several additional proteins of molecular weights 45,000 to > 92,500, possibly of host or viral origin. The RNA in each type of particle is a 35s molecule; T1 oligonucleotide fingerprint profiles suggest minor differences in the two RNAs. Hybridization experiments show a great deal of sequence homology between the RNA of the diabetogenic strain and the RNA of prototype CB4, which does not induce overt diabetes. MBVs are 10‐ 70 times less infective than virions, yet they are more pathogenic in mice and induce significantly higher glucose intolerance (hyperglycemia). The hyperglycemic response appears to be lower in mice infected with both types of particles than in mice infected with MBVs alone. Thus, the two subpopulations of virions present in the diabetogenic strain differ biochemically and in their ability to induce diabetes.