Spherical aggregates of coxsackie B4 virus particles in mouse pancreas

A high titer culture of Coxsackie B4 virus was used to induce pancreatitis in newborn mice. In animals sacrificed 1 or 2 days after intraperitoneal inoculation, we observed cytonecrosis consistent with picornaviral infection as well as necrosis indicative of pancreatitis. In addition, we observed aggregates of particles which seem to be Coxsackie B4 virus particles, some arranged in the typical picornaviral crystalloid lattice formation and others arranged into spherical masses approximately 102 nm in diameter. Depending upon the depth and orientation of section through the spherical aggregates, the particles were arranged into two patterns which were readily distinguishable. When the plane of section was through the center of the sphere, 10 particles circularly arranged around a dense particle core were observed. When the sphere was cut tangentially, the particles were arranged in a zig-zag pattern so that there were two concentric layers of at least 6 particles per layer, with no central core. Both crystalloid and spherical aggregates were observed free within acinocyte cytoplasm, and within autophagic vacuoles, cytosegresomes, and fine granular bodies of acinocytes, and within phagocytic vacuoles of macrophages. We conclude that the spherical aggregates represent a distinct crystalloid form of Coxsackie B4 virus during its replicative cycle, which may eventually develop into the more typical picornaviral crystalloid lattice configuration and that the spherical aggregates are located in foci of viral synthesis. Marked pathogenicity of Coxsackie B4 virus in the newborn mouse pancreas should be considered a factor in the observations noted.