Host range phenotype induced by mutations in the internal ribosomal entry site of poliovirus RNA.
Most poliovirus strains infect only primates. The host range (HR) of poliovirus is thought to be primarily determined by a cell surface molecule that functions as poliovirus receptor (PVR), since it has been shown that transgenic mice are made poliovirus sensitive by introducing the human PVR gene into the genome. The relative levels of neurovirulence of polioviruses tested in these transgenic mice were shown to correlate well with the levels tested in monkeys (H. Horie et al., J. Virol. 68:681-688, 1994). Mutants of the virulent Mahoney strain of poliovirus have been generated by disruption of nucleotides 128 to 134, at stem-loop II within the 5' noncoding region, and four of these mutants multiplicated well in human HeLa cells but poorly in mouse TgSVA cells that had been established from the kidney of the poliovirus-sensitive transgenic mouse. Neurovirulence tests using the two animal models revealed that these mutants were strongly attenuated only in tests with the mouse model and were therefore HR mutants. The virus infection cycle in TgSVA cells was restricted by an internal ribosomal entry site (IRES)-dependent initiation process of translation. Viral protein synthesis and the associated block of cellular protein synthesis were not observed in TgSVA cells infected with three of four HR mutants and was evident at only a low level in the remaining mutant. The mutant RNAs were functional in a cell-free protein synthesis system from HeLa cells but not in those from TgSVA and mouse neuroblastoma NS20Y cells. These results suggest that host factor(s) affecting IRES-dependent translation of poliovirus differ between human and mouse cells and that the mutant IRES constructs detect species differences in such host factor(s). The IRES could potentially be a host range determinant for poliovirus infection.
Shiroki
K
K
Department of Microbiology, Institute of Medical Science, University of Tokyo, Minatoku, Japan.
Ishii
T
T
Aoki
T
T
Ota
Y
Y
Yang
W X
WX
Komatsu
T
T
Ami
Y
Y
Arita
M
M
Abe
S
S
Hashizume
S
S
Nomoto
A
A
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000821:virology; D002460:Cell Line; D002474:Cell-Free System; D006367:HeLa Cells; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009690:Nucleic Acid Conformation; D010641:Phenotype; D017955:Poliovirus / Q000302:isolation & purification / Q000378:metabolism / Q000472:pathogenicity*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis / Q000737:chemistry; D012045:Regulatory Sequences, Nucleic Acid; D013116:Spinal Cord / Q000821:virology; D014764:Viral Proteins / Q000096:biosynthesis; D014774:Virulence
D012367:RNA, Viral; D014764:Viral Proteins