Eukaryotic translation initiation factor 4 gamma 1 and Polypyrimidine tract-binding protein 1 interaction with Poliovirus Sabin Internal Ribosome Entry Site (eIF4G-PTBP1-Sabin IRES complex)

The interaction between eukaryotic translation initiation factor 4 gamma 1 (eIF4G1) and polypyrimidine tract-binding protein 1 (PTBP1) with the Sabin Poliovirus Internal Ribosome Entry Site (IRES) is a fundamental mechanism underlying the attenuation of the Sabin vaccine strains (Guest et al., 2004, J Virol). Poliovirus initiates translation via a cap-independent mechanism where the IRES element in the 5' untranslated region recruits the 40S ribosomal subunit by binding host factors, including the scaffold protein eIF4G and IRES-transacting factors (ITAFs) like PTBP1 (Ochs et al., 2003, RNA). In the attenuated Sabin strains, point mutations within the IRES (e.g., at nucleotide 480 in Type 1) weaken the recruitment of these factors, particularly in neural tissues, leading to a failure in viral protein synthesis and a loss of neurovirulence (Gromeier et al., 1999, PNAS). This interaction is a key target for studying viral pathogenesis and ensuring the genetic stability of live-attenuated vaccines. While no small-molecule drugs are currently approved to target this specific complex, it is a primary focus for the design of next-generation synthetic vaccines and the development of broad-spectrum antivirals that disrupt viral IRES-host factor assemblies (Kauder et al., 2006, J Virol).

Other names

eIF4G-PTB-Sabin IRES complexPoliovirus Sabin IRES-host factor complexSabin IRES-ITAF interactioneIF4G1-PTBP1-IRES assembly

Inhibition of viral protein synthesis by disrupting the recruitment of the 40S ribosomal subunit to the viral RNA through interference with the assembly of the eIF4G-PTBP1-IRES complex.