Antigenic Variation Among Adenovirus Type 12 Strains.

Recent reports relative to the oncogenicity of adenovirus types 12 and 18 (Trentin, Yabe, and Taylor, Science 137:835, 1962; Huebner, Rowe, and Lane, Proc. Natl. Acad. Sci. U.S. 48:2051, 1962) have caused a renewed surge of interest in the adenovirus group. In addition to the prototype strain Huie, Huebner and co-workers investigated eight adenovirus type 12 strains, recovered from anal swabs of children, for their ability to produce tumors in hamsters. Strains were put through a limited number of KB lpassages after isolation in KB or HEp-2 cells. Four strains were also reisolated in primary human embryonic kidney cells and carried through one additional passage in the same cells. All were inoculated into newborn hamsters. Three of the eight field isolates produced tumors in hamsters identical to those produced by the Huie strain. The proven oncogenicity of at least four different strains of type 12 l)recludes the possibility that the ability to cause tumors in newborn hamsters is a property unique to the prototype. Although additional factors were involved, the apparent inability of five of eight field isolates to produce tumors questions the homogeneity of adenovirus type 12 strains. For this reason, eight laboratory strains of adenovirus type 12 were examined in cross-neutralization tests with "early" antisera to see whether any intratypic differences could be detected. The prototype Huie strain used in this investigation was obtained through the courtesy of Robert J. Huebner, Laboratory of Infectious Disease, National Institutes of Health, Bethesda, Md. All other strains studied were obtained from Klaus Schell, MIicrobiological Associates, Inc., Bethesda, MId. In oui laboratory, viruses were lput through a limited number of passages in HeLa cells free from pleuropneumonia-like organisms, and a working stock pool produced in the same cells. Virus pools were identified as adenovirus type 12 by use of the following criteria: (i) presence of a soluble adenovirus group CF antigen when tested against specific convalescent human serum; (ii) inability to agglutinate rat, Rhesus monkey, or African Green monkey erythrocytes; (iii) inhibition of cytopathic effects (CPE) in HeLa cells by type 12 (Huie) hyperimmune serum but not by type 18. Antisera were prepared by a method previously described (Rafajko, Proc. Soc. Exptl. Biol. Med. 113:238, 1963) in which rabbits received a single intravenous inoculation of 1.5 ml of undiluted virus. Animals were exsanguinated 1 week later by cardiac puncture. Neutralization tests were carried out in 24-hrold HeLa tube cultures. Cells were planted in minimal essenitial medium with 10% agamma calf serum (Hv-land Laboratories, Los Angeles,