Analysis of the reversion to the neurovirulent genotype in attenuated polio vaccine viruses passaged in cultivation cells derived from the human alimentary tract

[Background] It is known that the attenuated polio vaccine viruses derived from oral poliovirus vaccine undergo neurovirulent reversion during repeated replication in the human alimentary tract, and some paralytic cases caused by the revertants have been reported. Furthermore, the revertants are excreted with the feces into the environment, and the viruses have caused new epidemics of poliomyelitis in the world. It is an obstacle for the achievement of polio eradication program. [Objective] In this study, to elucidate the reversion mechanism of polio vaccine virus to the neurovirulent genotype in the human alimentary tract, an accumulation of the reversion of the vaccine viruses passaged in cultivation cells which were derived from the human alimentary tract was analyzed. [Methods] Polio vaccine viruses were passaged three times in Caco-2 cells derived from human colon carcinoma. The reversion of the passaged viruses was analyzed by the MAPREC method designated to estimate the ratio of revertants in a virus population. [Results] The accumulation of reversion in the vaccine viruses increased rapidly with viruses passaged at a temperature of 37℃ compared with those at 34℃. However, it was hardly observed in viruses passaged in HEp-2 cells which were derived from human laryngeal carcinoma at a temperature of 37℃. [Conclusion] A large difference was observed in the frequency of reversion between Caco-2 and HEp-2 cells though both cells were derived from human carcinoma. It is important to elucidate the cellular factors which take part in the reversion frequency of the virus genome. Such research is expected to lead to the elucidation of the reversion mechanism and to the development of a controlling expedient for the neurovirulent reversion of the polio vaccine virus.