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Published in: Virology Journal 1/2023

Open Access 01-12-2023 | Case Report

PREB inhibits the replication of prototype foamy virus by affecting its transcription

Authors: Junshi Zhang, Yali Xu, Chenchen Wang, Xiaopeng Tuo, Xingli Zhao, Wentao Qiao, Juan Tan

Published in: Virology Journal | Issue 1/2023

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Abstract

Background

Foamy viruses (FVs) are unique nonpathogenic retroviruses, which remain latent in the host for a long time. Therefore, they may be safe, effective gene transfer vectors. In this study, were assessed FV–host cell interactions and the molecular mechanisms underlying FV latent infection.

Methods

We used the prototype FV (PFV) to infect HT1080 cells and a PFV indicator cell line (PFVL) to measure virus titers. After 48 h of infection, the culture supernatant (i.e., cell-free PFV particles) and transfected cells (i.e., cell-associated PFV particles) were harvested and incubated with PFVL. After another 48 h, the luciferase activity was used to measure virus titers.

Results

Through transcriptomics sequencing, we found that PREB mRNA expression was significantly upregulated. Moreover, PREB overexpression reduced PFV replication, whereas endogenous PREB knockdown increased PFV replication. PREB interacted with the Tas DNA-binding and transcriptional activation domains and interfered with its binding to the PFV long terminal repeat and internal promoter, preventing the recruitment of transcription factors and thereby inhibiting the transactivation function of Tas. PREB C-terminal 329–418 aa played a major role in inhibiting PFV replication; PREB also inhibited bovine FV replication. Therefore, PREB has a broad-spectrum inhibitory effect on FV replication.

Conclusions

Our results demonstrated that PREB inhibits PFV replication by impeding its transcription.
Appendix
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Literature
1.
go back to reference Enders JF, Peebles TC. Propagation in tissue cultures of cytopathogenic agents from patients with Measles. Proc Soc Exp Biol Med. 1954;86:277–86.PubMedCrossRef Enders JF, Peebles TC. Propagation in tissue cultures of cytopathogenic agents from patients with Measles. Proc Soc Exp Biol Med. 1954;86:277–86.PubMedCrossRef
2.
go back to reference Mergia A. Simian foamy virus type 1 contains a second promoter located at the 3’ end of the env gene. Virology. 1994;199:219–22.PubMedCrossRef Mergia A. Simian foamy virus type 1 contains a second promoter located at the 3’ end of the env gene. Virology. 1994;199:219–22.PubMedCrossRef
5.
go back to reference Meiering CD, Linial ML. Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein. Proc Natl Acad Sci USA. 2002;99:15130–5.PubMedPubMedCentralCrossRef Meiering CD, Linial ML. Reactivation of a complex retrovirus is controlled by a molecular switch and is inhibited by a viral protein. Proc Natl Acad Sci USA. 2002;99:15130–5.PubMedPubMedCentralCrossRef
7.
go back to reference Mergia A, Renshaw-Gegg LW, Stout MW, Renne R, Herchenroeder O. Functional domains of the simian foamy virus type 1 transcriptional transactivator (Taf). J Virol. 1993;67:4598–604.PubMedPubMedCentralCrossRef Mergia A, Renshaw-Gegg LW, Stout MW, Renne R, Herchenroeder O. Functional domains of the simian foamy virus type 1 transcriptional transactivator (Taf). J Virol. 1993;67:4598–604.PubMedPubMedCentralCrossRef
8.
go back to reference Regad T, Saib A, Lallemand-Breitenbach V, Pandolfi PP, de The H, Chelbi-Alix MK. PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. EMBO J. 2001;20:3495–505.PubMedPubMedCentralCrossRef Regad T, Saib A, Lallemand-Breitenbach V, Pandolfi PP, de The H, Chelbi-Alix MK. PML mediates the interferon-induced antiviral state against a complex retrovirus via its association with the viral transactivator. EMBO J. 2001;20:3495–505.PubMedPubMedCentralCrossRef
9.
go back to reference Dong LL, Cheng QQ, Wang ZH, Yuan PP, Li Z, Sun Y, Han S, Yin J, Peng BW, He XH, Liu WH. Human Pirh2 is a novel inhibitor of Prototype Foamy Virus Replication. Viruses-Basel. 2015;7:1668–84.CrossRef Dong LL, Cheng QQ, Wang ZH, Yuan PP, Li Z, Sun Y, Han S, Yin J, Peng BW, He XH, Liu WH. Human Pirh2 is a novel inhibitor of Prototype Foamy Virus Replication. Viruses-Basel. 2015;7:1668–84.CrossRef
10.
go back to reference Tan J, Qiao WT, Wang J, Xu FW, Li Y, Zhou J, Chen QM, Geng YQ. IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus. J Virol. 2008;82:4275–83.PubMedPubMedCentralCrossRef Tan J, Qiao WT, Wang J, Xu FW, Li Y, Zhou J, Chen QM, Geng YQ. IFP35 is involved in the antiviral function of interferon by association with the viral tas transactivator of bovine foamy virus. J Virol. 2008;82:4275–83.PubMedPubMedCentralCrossRef
11.
go back to reference Hu X, Yang W, Liu R, Geng Y, Qiao W, Tan J. N-Myc interactor inhibits prototype foamy virus by sequestering viral tas protein in the cytoplasm. J Virol. 2014;88:7036–44.PubMedPubMedCentralCrossRef Hu X, Yang W, Liu R, Geng Y, Qiao W, Tan J. N-Myc interactor inhibits prototype foamy virus by sequestering viral tas protein in the cytoplasm. J Virol. 2014;88:7036–44.PubMedPubMedCentralCrossRef
12.
go back to reference Zhang J, Han C, Xiong Z, Qiu M, Tuo X, Wang C, Qiao W, Tan J. SGK1, a Serine/Threonine kinase, inhibits Prototype Foamy Virus Replication. Microbiol Spectr. 2022;10:e0199521.PubMedCrossRef Zhang J, Han C, Xiong Z, Qiu M, Tuo X, Wang C, Qiao W, Tan J. SGK1, a Serine/Threonine kinase, inhibits Prototype Foamy Virus Replication. Microbiol Spectr. 2022;10:e0199521.PubMedCrossRef
13.
go back to reference LaPointe P, Gurkan C, Balch WE. Mise en place-this bud’s for the Golgi. Mol Cell. 2004;14:413–4.PubMedCrossRef LaPointe P, Gurkan C, Balch WE. Mise en place-this bud’s for the Golgi. Mol Cell. 2004;14:413–4.PubMedCrossRef
14.
go back to reference Fliss MS, Hinkle PM, Bancroft C. Expression cloning and characterization of PREB (prolactin regulatory element binding), a novel WD motif DNA-binding protein with a capacity to regulate prolactin promoter activity. Mol Endocrinol. 1999;13:644–57.PubMedCrossRef Fliss MS, Hinkle PM, Bancroft C. Expression cloning and characterization of PREB (prolactin regulatory element binding), a novel WD motif DNA-binding protein with a capacity to regulate prolactin promoter activity. Mol Endocrinol. 1999;13:644–57.PubMedCrossRef
15.
go back to reference Weissman JT, Plutner H, Balch WE. The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export. Traffic. 2001;2:465–75.PubMedCrossRef Weissman JT, Plutner H, Balch WE. The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export. Traffic. 2001;2:465–75.PubMedCrossRef
16.
go back to reference Neer EJ, Schmidt CJ, Nambudripad R, Smith TF. The ancient regulatory-protein family of WD-repeat proteins. Nature. 1994;371:297–300.PubMedCrossRef Neer EJ, Schmidt CJ, Nambudripad R, Smith TF. The ancient regulatory-protein family of WD-repeat proteins. Nature. 1994;371:297–300.PubMedCrossRef
17.
go back to reference Ohtsuka S, Murao K, Imachi H, Cao WM, Yu X, Li J, Iwama H, Wong NC, Bancroft C, Ishida T. Prolactin regulatory element binding protein as a potential transcriptional factor for the insulin gene in response to glucose stimulation. Diabetologia. 2006;49:1599–607.PubMedCrossRef Ohtsuka S, Murao K, Imachi H, Cao WM, Yu X, Li J, Iwama H, Wong NC, Bancroft C, Ishida T. Prolactin regulatory element binding protein as a potential transcriptional factor for the insulin gene in response to glucose stimulation. Diabetologia. 2006;49:1599–607.PubMedCrossRef
18.
go back to reference Yu X, Murao K, Imachi H, Li J, Nishiuchi T, Dobashi H, Hosomi N, Masugata H, Zhang GX, Iwama H, Ishida T. The transcription factor prolactin regulatory element-binding protein mediates prolactin transcription induced by thyrotropin-releasing hormone in GH3 cells. Endocrine. 2010;38:53–9.PubMedCrossRef Yu X, Murao K, Imachi H, Li J, Nishiuchi T, Dobashi H, Hosomi N, Masugata H, Zhang GX, Iwama H, Ishida T. The transcription factor prolactin regulatory element-binding protein mediates prolactin transcription induced by thyrotropin-releasing hormone in GH3 cells. Endocrine. 2010;38:53–9.PubMedCrossRef
19.
go back to reference Imachi H, Murao K, Cao WM, Muraoka T, Nishiuchi T, Dobashi H, Hosomi N, Iwama H, Ishida T. The prolactin regulatory element-binding regulates of the 11beta-hydroxylase gene. Biochem Biophys Res Commun. 2008;376:531–5.PubMedCrossRef Imachi H, Murao K, Cao WM, Muraoka T, Nishiuchi T, Dobashi H, Hosomi N, Iwama H, Ishida T. The prolactin regulatory element-binding regulates of the 11beta-hydroxylase gene. Biochem Biophys Res Commun. 2008;376:531–5.PubMedCrossRef
20.
go back to reference Murao K, Imachi H, Yu X, Cao WM, Muraoka T, Dobashi H, Hosomi N, Haba R, Iwama H, Ishida T. The transcriptional factor prolactin regulatory element-binding protein mediates the gene transcription of adrenal scavenger receptor class B type I via 3’,5’-cyclic adenosine 5’-monophosphate. Endocrinology. 2008;149:6103–12.PubMedCrossRef Murao K, Imachi H, Yu X, Cao WM, Muraoka T, Dobashi H, Hosomi N, Haba R, Iwama H, Ishida T. The transcriptional factor prolactin regulatory element-binding protein mediates the gene transcription of adrenal scavenger receptor class B type I via 3’,5’-cyclic adenosine 5’-monophosphate. Endocrinology. 2008;149:6103–12.PubMedCrossRef
21.
go back to reference Park JM, Kim MY, Kim TH, Min DK, Yang GE, Ahn YH. Prolactin regulatory element-binding (PREB) protein regulates hepatic glucose homeostasis. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2097–107.PubMedCrossRef Park JM, Kim MY, Kim TH, Min DK, Yang GE, Ahn YH. Prolactin regulatory element-binding (PREB) protein regulates hepatic glucose homeostasis. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2097–107.PubMedCrossRef
22.
go back to reference Kong L, Fujimoto A, Nakamura M, Aoyagi H, Matsuda M, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, et al. Prolactin Regulatory element binding protein is involved in Hepatitis C Virus Replication by Interaction with NS4B. J Virol. 2016;90:3093–111.PubMedPubMedCentralCrossRef Kong L, Fujimoto A, Nakamura M, Aoyagi H, Matsuda M, Watashi K, Suzuki R, Arita M, Yamagoe S, Dohmae N, et al. Prolactin Regulatory element binding protein is involved in Hepatitis C Virus Replication by Interaction with NS4B. J Virol. 2016;90:3093–111.PubMedPubMedCentralCrossRef
23.
go back to reference Durocher Y, Perret S, Kamen A. High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells. Nucleic Acids Res. 2002;30:E9.PubMedPubMedCentralCrossRef Durocher Y, Perret S, Kamen A. High-level and high-throughput recombinant protein production by transient transfection of suspension-growing human 293-EBNA1 cells. Nucleic Acids Res. 2002;30:E9.PubMedPubMedCentralCrossRef
24.
go back to reference Life RB, Lee EG, Eastman SW, Linial ML. Mutations in the amino terminus of foamy virus gag disrupt morphology and infectivity but do not target assembly. J Virol. 2008;82:6109–19.PubMedPubMedCentralCrossRef Life RB, Lee EG, Eastman SW, Linial ML. Mutations in the amino terminus of foamy virus gag disrupt morphology and infectivity but do not target assembly. J Virol. 2008;82:6109–19.PubMedPubMedCentralCrossRef
25.
go back to reference Zhang J, Wang C, Tuo X, Chai K, Xu Y, Qiao W, Tan J. Prototype foamy virus downregulates RelB expression to facilitate viral replication. FEBS Open Bio. 2020;10:2137–48.PubMedPubMedCentralCrossRef Zhang J, Wang C, Tuo X, Chai K, Xu Y, Qiao W, Tan J. Prototype foamy virus downregulates RelB expression to facilitate viral replication. FEBS Open Bio. 2020;10:2137–48.PubMedPubMedCentralCrossRef
26.
go back to reference Bing T, Yu H, Li Y, Sun L, Tan J, Geng Y, Qiao W. Characterization of a full-length infectious clone of bovine foamy virus 3026. Virol Sin. 2014;29:94–102.PubMedPubMedCentralCrossRef Bing T, Yu H, Li Y, Sun L, Tan J, Geng Y, Qiao W. Characterization of a full-length infectious clone of bovine foamy virus 3026. Virol Sin. 2014;29:94–102.PubMedPubMedCentralCrossRef
27.
go back to reference Wang J, Guo HY, Jia R, Xu X, Tan J, Geng YQ, Qiao WT. Preparation of BFV Gag antiserum and preliminary study on cellular distribution of BFV. Virol Sin. 2010;25:115–22.PubMedPubMedCentralCrossRef Wang J, Guo HY, Jia R, Xu X, Tan J, Geng YQ, Qiao WT. Preparation of BFV Gag antiserum and preliminary study on cellular distribution of BFV. Virol Sin. 2010;25:115–22.PubMedPubMedCentralCrossRef
28.
go back to reference Tai HY, Sun KH, Kung SH, Liu WT. A quantitative assay for measuring human foamy virus using an established indicator cell line. J Virol Methods. 2001;94:155–62.PubMedCrossRef Tai HY, Sun KH, Kung SH, Liu WT. A quantitative assay for measuring human foamy virus using an established indicator cell line. J Virol Methods. 2001;94:155–62.PubMedCrossRef
29.
go back to reference Kretzschmar B, Nowrouzi A, Hartl MJ, Gartner K, Wiktorowicz T, Herchenroder O, Kanzler S, Rudolph W, Mergia A, Wohrl B, Rethwilm A. AZT-resistant foamy virus. Virology. 2008;370:151–7.PubMedCrossRef Kretzschmar B, Nowrouzi A, Hartl MJ, Gartner K, Wiktorowicz T, Herchenroder O, Kanzler S, Rudolph W, Mergia A, Wohrl B, Rethwilm A. AZT-resistant foamy virus. Virology. 2008;370:151–7.PubMedCrossRef
30.
go back to reference Hare S, Vos AM, Clayton RF, Thuring JW, Cummings MD, Cherepanov P. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A. 2010;107:20057–62.PubMedPubMedCentralCrossRef Hare S, Vos AM, Clayton RF, Thuring JW, Cummings MD, Cherepanov P. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A. 2010;107:20057–62.PubMedPubMedCentralCrossRef
31.
go back to reference Delelis O, Brussel A, Sonigo P. Quantification of HFV-integrated DNA in human cells by Alu-LTR real-time PCR. Methods Mol Biol. 2005;304:155–70.PubMed Delelis O, Brussel A, Sonigo P. Quantification of HFV-integrated DNA in human cells by Alu-LTR real-time PCR. Methods Mol Biol. 2005;304:155–70.PubMed
32.
go back to reference Yap MW, Lindemann D, Stanke N, Reh J, Westphal D, Hanenberg H, Ohkura S, Stoye JP. Restriction of foamy viruses by primate Trim5alpha. J Virol. 2008;82:5429–39.PubMedPubMedCentralCrossRef Yap MW, Lindemann D, Stanke N, Reh J, Westphal D, Hanenberg H, Ohkura S, Stoye JP. Restriction of foamy viruses by primate Trim5alpha. J Virol. 2008;82:5429–39.PubMedPubMedCentralCrossRef
33.
go back to reference Delebecque F, Suspene R, Calattini S, Casartelli N, Saib A, Froment A, Wain-Hobson S, Gessain A, Vartanian JP, Schwartz O. Restriction of foamy viruses by APOBEC cytidine deaminases. J Virol. 2006;80:605–14.PubMedPubMedCentralCrossRef Delebecque F, Suspene R, Calattini S, Casartelli N, Saib A, Froment A, Wain-Hobson S, Gessain A, Vartanian JP, Schwartz O. Restriction of foamy viruses by APOBEC cytidine deaminases. J Virol. 2006;80:605–14.PubMedPubMedCentralCrossRef
34.
go back to reference Guo G, Wang Y, Hu XM, Li ZR, Tan J, Qiao WT. Human Schlafen 11 exploits codon preference discrimination to attenuate viral protein synthesis of prototype foamy virus (PFV). Virology. 2021;555:78–88.PubMedCrossRef Guo G, Wang Y, Hu XM, Li ZR, Tan J, Qiao WT. Human Schlafen 11 exploits codon preference discrimination to attenuate viral protein synthesis of prototype foamy virus (PFV). Virology. 2021;555:78–88.PubMedCrossRef
38.
go back to reference Yan J, Zheng Y, Yuan P, Wang S, Han S, Yin J, Peng B, Li Z, Sun Y, He X, Liu W. Novel host protein TBC1D16, a GTPase activating protein of Rab5C, inhibits Prototype Foamy Virus Replication. Front Immunol. 2021;12:658660.PubMedPubMedCentralCrossRef Yan J, Zheng Y, Yuan P, Wang S, Han S, Yin J, Peng B, Li Z, Sun Y, He X, Liu W. Novel host protein TBC1D16, a GTPase activating protein of Rab5C, inhibits Prototype Foamy Virus Replication. Front Immunol. 2021;12:658660.PubMedPubMedCentralCrossRef
39.
go back to reference Wagner A, Doerks A, Aboud M, Alonso A, Tokino T, Flugel RM, Lochelt M. Induction of cellular genes is mediated by the Bel1 transactivator in foamy virus-infected human cells. J Virol. 2000;74:4441–7.PubMedPubMedCentralCrossRef Wagner A, Doerks A, Aboud M, Alonso A, Tokino T, Flugel RM, Lochelt M. Induction of cellular genes is mediated by the Bel1 transactivator in foamy virus-infected human cells. J Virol. 2000;74:4441–7.PubMedPubMedCentralCrossRef
40.
go back to reference Yuan PP, Yan J, Wang S, Guo Y, Xi XY, Han S, Yin J, Peng BW, He XH, Bodem J, Liu WH. Trim28 acts as restriction factor of prototype foamy virus replication by modulating H3K9me3 marks and destabilizing the viral transactivator tas. Retrovirology 2021, 18. Yuan PP, Yan J, Wang S, Guo Y, Xi XY, Han S, Yin J, Peng BW, He XH, Bodem J, Liu WH. Trim28 acts as restriction factor of prototype foamy virus replication by modulating H3K9me3 marks and destabilizing the viral transactivator tas. Retrovirology 2021, 18.
41.
go back to reference Ohtsuka S, Murao K, Imachi H, Cao WM, Yu X, Li J, Iwama H, Wong NCW, Bancroft C, Ishida T. Prolactin regulatory element binding protein as a potential transcriptional factor for the insulin gene in response to glucose stimulation. Diabetologia. 2006;49:1599–607.PubMedCrossRef Ohtsuka S, Murao K, Imachi H, Cao WM, Yu X, Li J, Iwama H, Wong NCW, Bancroft C, Ishida T. Prolactin regulatory element binding protein as a potential transcriptional factor for the insulin gene in response to glucose stimulation. Diabetologia. 2006;49:1599–607.PubMedCrossRef
42.
go back to reference Dong L, Cheng Q, Wang Z, Yuan P, Li Z, Sun Y, Han S, Yin J, Peng B, He X, Liu W. Human Pirh2 is a novel inhibitor of prototype foamy virus replication. Viruses. 2015;7:1668–84.PubMedPubMedCentralCrossRef Dong L, Cheng Q, Wang Z, Yuan P, Li Z, Sun Y, Han S, Yin J, Peng B, He X, Liu W. Human Pirh2 is a novel inhibitor of prototype foamy virus replication. Viruses. 2015;7:1668–84.PubMedPubMedCentralCrossRef
Metadata
Title
PREB inhibits the replication of prototype foamy virus by affecting its transcription
Authors
Junshi Zhang
Yali Xu
Chenchen Wang
Xiaopeng Tuo
Xingli Zhao
Wentao Qiao
Juan Tan
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2023
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-023-02211-y

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