Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Virus-induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members are not Required for the Efficient Replication of HSV-1

Version 1 : Received: 24 May 2022 / Approved: 26 May 2022 / Online: 26 May 2022 (10:34:09 CEST)

A peer-reviewed article of this Preprint also exists.

Zubković, A.; Žarak, I.; Ratkaj, I.; Rokić, F.; Jekić, M.; Pribanić Matešić, M.; Lebrón, R.; Gómez-Martín, C.; Lisnić, B.; Lisnić, V.J.; Jonjić, S.; Pan, D.; Vugrek, O.; Hackenberg, M.; Jurak, I. The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1. Viruses 2022, 14, 1661. Zubković, A.; Žarak, I.; Ratkaj, I.; Rokić, F.; Jekić, M.; Pribanić Matešić, M.; Lebrón, R.; Gómez-Martín, C.; Lisnić, B.; Lisnić, V.J.; Jonjić, S.; Pan, D.; Vugrek, O.; Hackenberg, M.; Jurak, I. The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1. Viruses 2022, 14, 1661.

Abstract

Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of regulation of efficient virus replication. In this study, we comprehen-sively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182 are reproducibly deregulated dur-ing productive infection. These miRNAs are predicted to regulate a great number of potential tar-gets involved in different cellular processes and have only 33 shared targets. Among these, mem-bers of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.

Keywords

herpes simplex virus 1; HSV-1; virus-host interaction; miRNA; FoxO

Subject

Biology and Life Sciences, Virology

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