Eukaryotic translation initiation factor 4 gamma 1 (eIF4G1) (eIF4G1)

Eukaryotic translation initiation factor 4 gamma 1 (eIF4G1) is a large scaffolding protein that serves as a central component of the eIF4F complex, which is essential for recruiting the 40S ribosomal subunit to mRNA (UniProt Consortium, 2023). In the context of poliovirus type 3 infection, the virus utilizes an Internal Ribosome Entry Site (IRES) within its 5' untranslated region to hijack the host's translation machinery. Specifically, domain V of the poliovirus IRES directly interacts with the C-terminal fragment of eIF4G1 to facilitate cap-independent translation of the viral genome (de Breyne et al., 2009). This interaction is critical because the viral 2A protease cleaves eIF4G1, effectively halting host cap-dependent translation while leaving the eIF4G1 fragment necessary for viral synthesis intact (Pestova et al., 1996). Targeting the eIF4G1-IRES interaction or the broader eIF4F complex represents a potential therapeutic strategy to inhibit viral replication (Cencic et al., 2011). However, because eIF4G1 is vital for normal cellular protein synthesis, achieving high selectivity for viral translation over host translation remains a significant therapeutic challenge (Thompson, 2012).

Other names

eIF4GeIF-4G1p220Eukaryotic translation initiation factor 4 gammaEIF4G1

Inhibition of the eIF4F complex assembly or direct disruption of the eIF4G-IRES domain V interaction to block viral translation initiation.