Phospho-eIF4E stimulation regulates coronavirus entry by selective expression of cell membrane-residential factors

The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E. We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43. Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.

Background:

The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation. In our previous study, several host factors susceptible to a high level of p-eIF4E were found to be conducive to viral infection by coronavirus PEDV. The current paper is focused on cell membrane-residential factors, which are involved in signal pathways that are sensitive to phosphorylated eIF4E.

Methods:

The abstract does not provide specific methodology details, but the study involved analyses of phosphorylation pathways, translation and transcription levels, and viral entry assays for multiple coronaviruses (PEDV, SARS-CoV, SARS-CoV-2, HCoV-OC43).

Results:

We found that the ERK-MNK pathway was activated, which resulted in the stimulation of phosphorylation of eIF4E in early PEDV infection. Phospho-eIF4E promoted the viral invasion of PEDV by upregulating the expression of host factors TSPAN3, CD63, and ITGB2 at the translation level rather than at the transcription level. Moreover, TSPAN3, CD63, or ITGB2 facilitates the efficient entry of coronavirus SARS-CoV, SARS-CoV-2, and HCoV-OC43.

Data Summary:

The study identifies TSPAN3, CD63, and ITGB2 as host factors upregulated at the translation level by phospho-eIF4E. These factors facilitate entry of PEDV, SARS-CoV, SARS-CoV-2, and HCoV-OC43. No quantitative statistics are provided in the abstract.

Conclusions:

Our findings broaden our insights into the dynamic phosphorylation of eIF4E during the viral life cycle, and provide further evidence that phosphorylated eIF4E regulates selective translation of host mRNA.

Practical Significance:

The findings suggest potential targets for antiviral interventions, such as the ERK-MNK-eIF4E pathway or the host factors TSPAN3, CD63, and ITGB2, which may have real-world applications in developing therapies against coronavirus infections.