Hijacking the translation apparatus by RNA viruses

Abstract

As invading viruses do not harbor functional ribosomes in their virions, successful amplification of the viral genomes requires that viral mRNAs compete with cellular mRNAs for the host cell translation apparatus. Several RNA viruses have evolved remarkable strategies to recruit the host translation initiation factors required for the first steps in translation initiation by host cell mRNAs. This review describes the ways that three families of RNA viruses effectively usurp limiting translation initiation factors from the host.

Figure 1.

Model depicting the major participants that are involved in translational initiation in eukaryotic mRNAs. Interactions of eukaryotic translation initiation factors eIF2 (2), eIF3 (3), and initiator tRNA with a 40S ribosomal subunit, eIF4E (4E), eIF4A (4A), and eIF4G (4G) with the m⁷G cap structure, and the polyadenosine binding protein PABP with the polyadenosine tail in an mRNA are shown.

Figure 2.

Alterations of the cap binding protein complex eIF4F in infected cells. (Top) Cleavage of eIF4G by picornaviral proteases. (Middle) Sequestration of eIF4E by 4E binding proteins (4E-BP) due to dephosphorylation of 4E-BPs in picornavirus-infected cells. (Bottom) Eviction of PABP by viral NSP3 from the cap binding protein complex eIF4F in rotavirus- infected cells. Interactions of eukaryotic initiation factors eIF4G (4G), eIF4A (4A), eIF4E (4E), and eIF3 (3) are indicated.

Figure 3.

Occupation of the ribosomal P-site by the cricket paralysis virus IRES. Basepair interactions between sequences in the viral IRES positioned in the ribosomal P-site (P) are diagramed. An empty ribosomal A-site (A) that can accept the first elongator tRNA molecule is shown.