Host translation initiation factors interacting with poliovirus IRES domain V (eIF4G-IRES Domain V complex)

Domain V of the poliovirus internal ribosome entry site (IRES) is a critical RNA structure that recruits host translation initiation factors to facilitate cap-independent viral protein synthesis. The primary host factors involved are the eIF4G/eIF4A complex, which binds to the lower part of Domain V, and eIF4B, which binds to the upper part. Additionally, glycyl-tRNA synthetase (GARS) and the cold shock domain-containing protein E1 (UNR/CSDE1) interact with the apical region of Domain V to stabilize the initiation complex and promote 40S ribosomal subunit recruitment. Mutations in Domain V, such as those found in the Sabin vaccine strains, impair these interactions and are major determinants of viral attenuation and neurovirulence. Targeting this interaction with small molecules or nucleic acid-based therapies represents a strategy for developing antivirals against poliovirus and related enteroviruses. Experimental inhibitors include eIF4A inhibitors like silvestrol and hippuristanol, which prevent the necessary RNA unwinding for ribosome entry, as well as antisense oligonucleotides that sterically block host factor binding sites. While effective in suppressing viral replication, therapeutic challenges include the potential for off-target effects on cellular mRNAs that utilize IRES-mediated translation and the high mutation rate of the viral genome.

Other names

Poliovirus IRES Domain V binding proteinsIRES trans-acting factors (ITAFs) for PolioviruseIF4G/eIF4A/eIF4B/GARS/UNR complexPoliovirus IRES-host factor interaction

Inhibition of viral translation by blocking the recruitment of the 40S ribosomal subunit or disrupting the interaction between host factors and the IRES Domain V.