RIOK3-Mediated Akt phosphorylation facilitates synergistic replication of Marek’s disease and reticuloendotheliosis viruses

ABSTRACT

Co-infection of Marek’s disease virus (MDV) and reticuloendotheliosis virus (REV) synergistically drives disease progression, yet little is known about the mechanism of the synergism. Here, we found that co-infection of REV and MDV increased their replication via the RIOK3-Akt pathway. Initially, we noticed that the viral titres of MDV and REV significantly increased in REV and MDV co-infected cells compared with single-infected cells. Furthermore, tandem mass tag peptide labelling coupled with LC/MS analysis showed that Akt was upregulated in REV and MDV co-infected cells. Overexpression of Akt promoted synergistic replication of MDV and REV. Conversely, inhibition of Akt suppressed synergistic replication of MDV and REV. However, PI3K inhibition did not affect synergistic replication of MDV and REV, suggesting that the PI3K/Akt pathway is not involved in the synergism of MDV and REV. In addition, we revealed that RIOK3 was recruited to regulate Akt in REV and MDV co-infected cells. Moreover, wild-type RIOK3, but not kinase-dead RIOK3, mediated Akt phosphorylation and promoted synergistic replication of MDV and REV. Our results illustrate that MDV and REV activated a novel RIOK3-Akt signalling pathway to facilitate their synergistic replication.

KEYWORDS:

• MDV
• REV
• synergistic replication
• RIOK3
• Akt

Acknowledgment

The work was supported by grants from the Shandong Modern Agricultural Technology & Industry System (No. SDAIT-11-04), the Natural Science Foundations of China (No. 32072816 and No. 31902233). We are grateful to Ms. Li Zhang for her advice and assistance. We thank Dr. Guihua Wang and Dr. Chengui Li for their helpful discussion.

Disclosure statement

The authors declare that they have no conflict of interest.

Author contributions

ZC and XD designed experiments; XD performed experiments, analysed data and wrote the manuscript; ZC conceived the study, wrote the manuscript and secured funding; DZ, JZ and JX provided techniques assistant. All authors read and approved the final version.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21505594.2022.2096247.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.