Isolation of rhinovirus intertypes related to either rhinoviruses 12 and 78 or 36 and 58.

Many antigenic relationships have been demonstrated among the 90 rhinovirus serotypes. Among these are reciprocal cross-reactions between serotypes 12 and 78 and between serotypes 36 and 58. Neutralizing-antibody titers to homologous virus of the related pairs are generally 16- to 64-fold higher than to the heterologous member, and neutralization by heterologous antiserum in the pools is not seen with prototype viruses. However, a number of isolates were encountered which gave anomolous results when tested with the antiserum pools in fetal tonsil cells. When these strains were tested in fetal tonsil cells against the monospecific antisera composing the pools, it was shown that several isolates were apparently intertypes, neutralized equally by antisera to related types 12 and 78 or 36 and 58. Isolate 1104, an apparent intertype between serotypes 36 and 58, and isolate 9433, intermediate between serotypes 12 and 78, were selected to use as immunogens in rabbits. When tested in HeLa cells, antiserum prepared against isolate 1104 neutralized isolates 1104, 58, and 36 at titers of 1280, 640, and 40, respectively. The k values against isolates 1104, 58, and 36 were 356, 145, and 4, respectively, indicating a much closer relationship of isolate 1104 to type 58 than to type 36. Similar results were obtained with isolate 9433. The neutralizing-antibody titer of anti-9433 serum was 160 against both 9433 and type 78 and was 20 against type 12. The k values of anti-9433 serum against 9433, 78, and 12 were 161, 111, and 2, respectively, indicating that 9433 and 78 were nearly identical. However, the respective neutralizing-antibody titers of anti-78 serum to type 78 and isolate 9433 were 640 and 80, and the respective k values were 172 and 85, demonstrating some antigenic differences. The discovery of intertypes confirms the antigenic variation among rhinoviruses, and the intertypes may represent links in the evolution of types. These observations also demonstrate that isolates in first or second passage in diploid cells may display an antigenic profile different from that seen in HeLa cells at high HeLa cell passage level.