The Eukaryotic Translation Initiation Factor 4F Complex Restricts Rotavirus Infection via Regulating the Expression of IRF1 and IRF7.

Abstract

The eIF4F complex is a translation initiation factor that closely regulates translation in response to a multitude of environmental conditions including viral infection. How translation initiation factors regulate rotavirus infection remains poorly understood. In this study, the knockdown of the components of the eIF4F complex using shRNA and CRISPR/Cas9 were performed, respectively. We have demonstrated that loss-of-function of the three components of eIF4F, including eIF4A, eIF4E and eIF4G, remarkably promotes the levels of rotavirus genomic RNA and viral protein VP4. Consistently, knockdown of the negative regulator of eIF4F and programmed cell death protein 4 (PDCD4) inhibits the expression of viral mRNA and the VP4 protein. Mechanically, we confirmed that the silence of the eIF4F complex suppressed the protein level of IRF1 and IRF7 that exert potent antiviral effects against rotavirus infection. Thus, these results demonstrate that the eIF4F complex is an essential host factor restricting rotavirus replication, revealing new targets for the development of new antiviral strategies against rotavirus infection.

• Authors: Sunrui Chen, Cui Feng, Yan Fang, Xinying Zhou, Lei Xu, Wenshi Wang, Xiangdong Kong, Maikel P Peppelenbosch, Qiuwei Pan, Yuebang Yin
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 7 (Mar 29 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30934842 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Apoptosis Regulatory Proteins
• Eukaryotic Initiation Factor-4F
• IRF1 protein, human
• IRF7 protein, human
• Interferon Regulatory Factor-1
• Interferon Regulatory Factor-7
• PDCD4 protein, human
• RNA-Binding Proteins

Topics

• Antiviral Agents (metabolism)
• Apoptosis Regulatory Proteins (metabolism)
• Caco-2 Cells
• Eukaryotic Initiation Factor-4F (metabolism)
• Gene Expression Regulation
• Gene Knockdown Techniques
• Gene Silencing
• Humans
• Interferon Regulatory Factor-1 (genetics, metabolism)
• Interferon Regulatory Factor-7 (genetics, metabolism)
• RNA-Binding Proteins (metabolism)
• Rotavirus Infections (genetics)