Dataset Information

Lnc-RP5 Regulates the miR-129-5p/Notch1/PFV Internal Promoter Axis to Promote the Expression of the Prototype Foamy Virus Transactivator Tas.

ABSTRACT: Prototype foamy virus (PFV) is a unique retrovirus that infects animals and humans and does not cause clinical symptoms. Long noncoding RNAs (lncRNAs) are believed to exert multiple regulatory functions during viral infections. Previously, we utilized RNA sequencing (RNA-seq) to characterize and identify the lncRNA lnc-RP5-1086D14.3.1-1:1 (lnc-RP5), which is markedly decreased in PFV-infected cells. However, little is known about the function of lnc-RP5 during PFV infection. In this study, we identified lnc-RP5 as a regulator of the PFV transcriptional transactivator (Tas). Lnc-RP5 enhanced the activity of the PFV internal promoter (IP). The expression of PFV Tas was found to be promoted by lnc-RP5. Moreover, miR-129-5p was found to be involved in the lnc-RP5-mediated promotion of PFV IP activity, while the Notch1 protein suppressed the activity of PFV IP and the expression of Tas. Our results demonstrate that lnc-RP5 promotes the expression of PFV Tas through the miR-129-5p/Notch1/PFV IP axis. This work provides evidence that host lncRNAs can manipulate PFV replication by employing miRNAs and proteins during an early viral infection.

SUBMITTER: Xu S

PROVIDER: S-EPMC7035397 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Lnc-RP5 Regulates the miR-129-5p/Notch1/PFV Internal Promoter Axis to Promote the Expression of the Prototype Foamy Virus Transactivator Tas.

Xu Shanshan S Chen Liujun L Tang Yinglian Y Yuan Peipei P Yan Jun J Zheng Yingcheng Y Huang Li L Li Zhi Z Sun Yan Y Han Song S Yin Jun J Pan Qin Q Peng Biwen B He Xiaohua X Liu Wanhong W

Virologica Sinica 20191021 1

Prototype foamy virus (PFV) is a unique retrovirus that infects animals and humans and does not cause clinical symptoms. Long noncoding RNAs (lncRNAs) are believed to exert multiple regulatory functions during viral infections. Previously, we utilized RNA sequencing (RNA-seq) to characterize and identify the lncRNA lnc-RP5-1086D14.3.1-1:1 (lnc-RP5), which is markedly decreased in PFV-infected cells. However, little is known about the function of lnc-RP5 during PFV infection. In this study, we id ...[more]

PMID: 31637632

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Project description:Foamy viruses (FVs) are complex retroviruses belonging to the Spumaretrovirinae subfamily of the Retroviridae family. In contrast to human immunodeficiency virus (HIV), another member of the Retroviridae family, FVs are nonpathogenic in their natural hosts or in experimentally infected animals. Prototype foamy virus (PFV) is the only foamy virus that can infect humans through cross-species transmission and does not show any pathogenicity after infection. Consequently, PFV is considered a safe and efficient gene transfer vector. Understanding the host proteins involved in the replication of PFV and the mechanism of interaction between the host and the virus might lead to studies to improve the efficiency of gene transfer. To date, only a few host factors have been identified that affect PFV replication. In the present study, we report that PFV infection enhances the promoter activity of SGK1 (encoding serum/glucocorticoid regulated kinase 1) via the Tas protein signaling pathway, and then upregulates the mRNA and protein levels of SGK1. Overexpression of SGK1 reduced PFV replication, whereas its depletion using small interfering RNA increased PFV replication. SGK1 inhibits PFV replication by impairing the function of the PFV Tas activation domain in a kinase-independent manner and reducing the stability of the Gag protein in a kinase-dependent manner. In addition, both human and bovine SGK1 proteins inhibit the replication of bovine foamy virus (BFV) and PFV. These findings not only improved our understanding of the function of SGK1 and its relationship with foamy viruses, but also contributed to determining the antiviral mechanism of the host. IMPORTANCE Foamy viruses can integrate into the host chromosome and are nonpathogenic in natural hosts or in experimentally infected animals. Therefore, foamy viruses are considered to be safe and efficient gene transfer vectors. Persistent infection of foamy viruses is partly caused by the restrictive effect of host factors on the virus. However, only a few cellular proteins are known to influence the replication of foamy viruses. In this study, we report that SGK1 inhibits the replication of prototype foamy virus by affecting the function of the transcription activator, Tas, and reducing the stability of the structural protein, Gag. These results will increase our understanding of the interaction between the virus and host factors, deepening our perception of host antiviral defenses and the function of SGK1, and could improve the gene transfer efficiency of foamy viruses.

Dataset Information

Lnc-RP5 Regulates the miR-129-5p/Notch1/PFV Internal Promoter Axis to Promote the Expression of the Prototype Foamy Virus Transactivator Tas.

Publications

Lnc-RP5 Regulates the miR-129-5p/Notch1/PFV Internal Promoter Axis to Promote the Expression of the Prototype Foamy Virus Transactivator Tas.

Similar Datasets

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