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.

On the Host Side of the Hepatitis E Virus Life Cycle

“…Among the different components, the eukaryotic translation initiation factor 4F (eIF4F) complex has been identified as being important for HEV replication. This complex is known to be involved in the cap-dependent translation and replication of several viruses (reviewed in [56]). In this context, an RNA interference-based loss-of-function study showed that components of the eIF4F complex are required for efficient HEV replication, while known negative regulatory factors of this pathway limit viral RNA synthesis [57].…”

RNA Helicases as Shadow Modulators of Cell Cycle Progression

“…In human breast adenocarcinoma cells, inhibition of eIF4A blocks cell cycle progression at the G1/S phase transition, likely through loss of Cyclin D1, Cyclin D2 and Cdk6, and induces apoptosis, in part, by inhibiting translation of BCL2. However, the main influence of eIF4A on cell cycle progression is contributed at the level of the translation initiation process [ 113 ]. Also, eIF4A is crucial for the translation of viral IRES mRNAs [ 114 ].…”

Flavaglines as natural products targeting eIF4A and prohibitins: From traditional Chinese medicine to antiviral activity against coronaviruses

“…Many viral mRNAs contain highly structured 5′-UTRs, suggesting that eIF4A inhibitors may block viral replication [ 21 ]. Indeed, Grünweller and collaborators found that silvestrol, at low nanomolar concentrations that are not toxic to cells, blocks viral mRNA translation and viral replication of Ebola virus and MERS-CoV in cells [ 6 , 7 ].…”

“…The importance of eIF4A during viral infections tends to be virus specific. In fact, viruses can either use it or not use it at all, or they may alternate between requiring and not requiring the eIF4A protein [ 21 ]. Several RNA viruses require eIF4A for the translation of their mRNAs, in particular those that are responsible for Ebola, chikungunya, hepatitis E, poliomyelitis, Zika fever, “hand, foot and mouth” disease, SARS, MERS and COVID-19 (recently reviewed in Ref.…”

“…Several RNA viruses require eIF4A for the translation of their mRNAs, in particular those that are responsible for Ebola, chikungunya, hepatitis E, poliomyelitis, Zika fever, “hand, foot and mouth” disease, SARS, MERS and COVID-19 (recently reviewed in Ref. [ 21 ]). As a consequence, eIF4A has emerged as a promising target to treat these viral infections and the use of compounds that inhibit the activity of eIF4A holds great interest as antiviral agents.…”