Eukaryotic initiation factor 4A (eIF4A) during viral infections

Abstract

The helicase eIF4A is part of the cellular eIF4F translation initiation complex. The main functions of eIF4A are to remove secondary complex structures within the 5'-untranslated region and to displace proteins attached to mRNA. As intracellular parasites, viruses regulate the processes involved in protein synthesis, and different mechanisms related to controlling translation factors, such as eIF4A, have been found. The inhibitors of this factor are currently known; these substances could be used in the near future as part of antiviral pharmacological therapies in instances of replication cycles in which eIF4A is required. In this review, the particularities of how some viruses make use of this initiation factor to synthesize their proteins are discussed.

Keywords: Initiation; Translation; Virus; eIF4A.

Fig. 1

Initiation of translation. 1 The eIF4F complex—which contains eIF4E, eIF4A, and eIF4G—2 recruits mRNA through the interaction of eIF4G with the poly(A)-binding protein (PABP), while eIF4E binds to the mRNA 5′ cap. 3 The 43S complex, which contains the small 40S ribosomal subunit, 4 binds eIF4G through eIF3 to carry out the scanning of the mRNA to the start codon, 5 and the full 80S ribosome is subsequently formed. Then the GDP-eIF2 complex is released and gives rise to the elongation phase

Fig. 2

Translational mechanisms of viral mRNAs that require eIF4A. a Cytomegalovirus protein pUL69 (CMV) ensures the recruitment of eIF4A into the eIF4F complex, making it more stable. b Influenza virus (IFV) employs a mechanism for the translation of its mRNAs that depends on eIF4A activity and the presence of eIF4G but not on the presence of eIF4E. c IRES in mRNAs of encephalomyocarditis virus (EMCV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and calicivirus (CV) are all dependent on eIF4A

Fig. 3

The eIF4A factor may not be necessary in some viral translation mechanisms. a Hantavirus codes for the N protein, which substitutes the function of the eIF4F complex. b Protein CpBV15β of Cotesia plutellae bracovirus (CpBV) has the task of sequestering eIF4A and thus inhibiting the formation of eIF4F. c Protease 3C, coded by the foot and mouth disease virus (FMDV), cuts eIF4A and eIF4G, which increases viral protein synthesis