Exchange of the internal ribosomal entry site (IRES) between poliovirus and human rhinovirus type 2 attenuates neurovirulence, which is cooperatively determined by two adjacent stem loop structures.
Two adjacent stem loop structures within the internal ribosomal entry site of poliovirus cooperatively control its neurovirulence in mammalian models.
In the human central nervous system, susceptibility to poliovirus (PV) infection is largely confined to a specific subpopulation of neuronal cells. PV tropism is likely to be determined by cell-external components such as the PV receptor CD155, as well as cell-internal constraints such as the availability of a suitable microenvironment for virus propagation. We reported previously that the exchange of the cognate internal ribosomal entry site (IRES) within the 5' nontranslated region of PV with its counterpart from human rhinovirus type 2 (HRV2) can eliminate the neuropathogenic phenotype in a transgenic mouse model for poliomyelitis without diminishing the growth properties in HeLa cells. We now show that attenuation of neurovirulence of PV/HRV2 chimeras is not confined to CD155 transgenic mice but is evident also after intraspinal inoculation into Cynomolgus monkeys. We have dissected the PV and HRV2 IRES elements to determine those structures responsible for neurovirulence (or attenuation) of these chimeric viruses. We report that two adjacent stem loop structures within the IRES cooperatively determine neuropathogenicity.
Gromeier et al. (Mon,) conducted a other in Poliovirus infection. Exchange of internal ribosomal entry site (IRES) elements vs. Wild-type poliovirus was evaluated on Neurovirulence / neuropathogenicity. Exchange of the internal ribosomal entry site (IRES) between poliovirus and human rhinovirus type 2 attenuates neurovirulence, which is cooperatively determined by two adjacent stem loop structures.