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Virology Journal
Published in: Virology Journal 1/2021

Open Access 01-12-2021 | Zika Virus | Research

IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3

Authors: Kai Ren, Ya Zhu, Honggang Sun, Shilin Li, Xiaoqiong Duan, Shuang Li, Yujia Li, Bin Li, Limin Chen

Published in: Virology Journal | Issue 1/2021

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Abstract

Background

Although interferon regulatory factor 2 (IRF2) was reported to stimulate virus replication by suppressing the type I interferon signaling pathway, because cell cycle arrest was found to promote viral replication, IRF2-regulated replication fork factor (FAM111A and RFC3) might be able to affect ZIKV replication. In this study, we aimed to investigate the function of IRF2, FAM111A and RFC3 to ZIKV replication and underlying mechanism.

Methods

siIRF2, siFAM111A, siRFC3 and pIRF2 in ZIKV-infected A549, 2FTGH and U5A cells were used to explore the mechanism of IRF2 to inhibit ZIKV replication. In addition, their expression was analyzed by RT-qPCR and western blots, respectively.

Results

In this study, we found IRF2 expression was increased in ZIKV-infected A549 cells and IRF2 inhibited ZIKV replication independent of type I IFN signaling pathway. IRF2 could activate FAM111A expression and then enhanced the host restriction effect of RFC3 to inhibit replication of ZIKV.

Conclusions

We speculated the type I interferon signaling pathway might not play a leading role in regulating ZIKV replication in IRF2-silenced cells. We found IRF2 was able to upregulate FAM111A expression and thus enhance the host restriction effect of RFC3 on ZIKV.
Literature
1.
Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, et al. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14:1232–9.PubMedPubMedCentralCrossRef
2.
Schuler-Faccini L, Sanseverino M, Vianna F, da Silva AA, Larrandaburu M, Marcolongo-Pereira C, et al. Zika virus: a new human teratogen? Implications for women of reproductive age. Clin Pharmacol Ther. 2016;100:28–30.PubMedCrossRef
3.
Bautista LE. Zika virus infection and risk of Guillain–Barre syndrome: a meta-analysis. J Neurol Sci. 2019;403:99–105.PubMedCrossRef
4.
Kuno G, Chang GJ. Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol. 2007;152:687–96.PubMedCrossRef
5.
Vieira C, Machado LC, Pena LJ, de Morais Bronzoni RV, Wallau GL. Spread of two Zika virus lineages in Midwest Brazil. Infect Genet Evol. 2019;75:103974.PubMedCrossRef
6.
Honda K, Taniguchi T. IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol. 2006;6:644–58.PubMedCrossRef
7.
Tamura T, Yanai H, Savitsky D, Taniguchi T. The IRF family transcription factors in immunity and oncogenesis. Annu Rev Immunol. 2008;26:535–84.PubMedCrossRef
8.
Chen YJ, Li J, Lu N, Shen XZ. Interferon regulatory factors: a key to tumour immunity. Int Immunopharmacol. 2017;49:1–5.PubMedCrossRef
9.
Taniguchi T, Ogasawara K, Takaoka A, Tanaka N. IRF family of transcription factors as regulators of host defense. Annu Rev Immunol. 2001;19:623–55.PubMedCrossRef
10.
Stone AE, Mitchell A, Brownell J, Miklin DJ, Golden-Mason L, Polyak SJ, et al. Hepatitis C virus core protein inhibits interferon production by a human plasmacytoid dendritic cell line and dysregulates interferon regulatory factor-7 and signal transducer and activator of transcription (STAT) 1 protein expression. PLoS ONE. 2014;9:e95627.PubMedPubMedCentralCrossRef
11.
12.
Frumence E, Roche M, Krejbich-Trotot P, El-Kalamouni C, Nativel B, Rondeau P, et al. The South Pacific epidemic strain of Zika virus replicates efficiently in human epithelial A549 cells leading to IFN-beta production and apoptosis induction. Virology. 2016;493:217–26.PubMedCrossRef
13.
Bordignon J, Probst CM, Mosimann AL, Pavoni DP, Stella V, Buck GA, et al. Expression profile of interferon stimulated genes in central nervous system of mice infected with dengue virus Type-1. Virology. 2008;377:319–29.PubMedCrossRef
14.
Kajaste-Rudnitski A, Mashimo T, Frenkiel MP, Guenet JL, Lucas M, Despres P. The 2’,5’-oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells. J Biol Chem. 2006;281:4624–37.PubMedCrossRef
15.
Liu K, Liao X, Zhou B, Yao H, Fan S, Chen P, et al. Porcine alpha interferon inhibit Japanese encephalitis virus replication by different ISGs in vitro. Res Vet Sci. 2013;95:950–6.PubMedCrossRef
16.
Harada H, Fujita T, Miyamoto M, Kimura Y, Maruyama M, Furia A, et al. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989;58:729–39.PubMedCrossRef
17.
Williams BR. Signal transduction and transcriptional regulation of interferon-alpha-stimulated genes. J Interf Res. 1991;11:207–13.CrossRef
18.
Williams BR. Transcriptional regulation of interferon-stimulated genes. Eur J Biochem. 1991;200:1–11.PubMedCrossRef
19.
Gu M, Lin G, Lai Q, Zhong B, Liu Y, Mi Y, et al. Ctenopharyngodon idella IRF2 plays an antagonistic role to IRF1 in transcriptional regulation of IFN and ISG genes. Dev Comp Immunol. 2015;49:103–12.PubMedCrossRef
20.
Sariyer IK, Gordon J, Burdo TH, Wollebo HS, Gianti E, Donadoni M, et al. Suppression of Zika virus infection in the brain by the antiretroviral drug rilpivirine. Mol Ther. 2019;27:2067–79.PubMedPubMedCentralCrossRef
21.
Panda D, Fernandez DJ, Lal M, Buehler E, Moss B. Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants. Proc Natl Acad Sci USA. 2017;114:3720–5.PubMedPubMedCentralCrossRef
22.
Alabert C, Bukowski-Wills JC, Lee SB, Kustatscher G, Nakamura K, de Lima AF, et al. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components. Nat Cell Biol. 2014;16:281–93.PubMedPubMedCentralCrossRef
23.
Fine DA, Rozenblatt-Rosen O, Padi M, Korkhin A, James RL, Adelmant G, et al. Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. PLoS Pathog. 2012;8:e1002949.PubMedPubMedCentralCrossRef
24.
Shen H, Xu J, Zhao S, Shi H, Yao S, Jiang N. ShRNA-mediated silencing of the RFC3 gene suppress ovarian tumor cells proliferation. Int J Clin Exp Pathol. 2015;8:8968–75.PubMedPubMedCentral
25.
Lutfalla G, Holland SJ, Cinato E, Monneron D, Reboul J, Rogers NC, et al. Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster. EMBO J. 1995;14:5100–8.PubMedPubMedCentralCrossRef
26.
Wang Y, Ren K, Li S, Yang C, Chen L. Interferon stimulated gene 15 promotes Zika virus replication through regulating Jak/STAT and ISGylation pathways. Virus Res. 2020;287:198087.PubMedCrossRef
27.
Ma W, Li S, Ma S, Jia L, Zhang F, Zhang Y, et al. Zika virus causes testis damage and leads to male infertility in mice. Cell. 2016;167:1511-1524 e1510.PubMedCrossRef
28.
Wu Y, Yang X, Yao Z, Dong X, Zhang D, Hu Y, et al. C19orf66 interrupts Zika virus replication by inducing lysosomal degradation of viral NS3. PLoS Negl Trop Dis. 2020;14:e0008083.PubMedPubMedCentralCrossRef
29.
Li J, Mao L, Zhong C, Li W, Hao F, Sun M, et al. Cellular microRNA bta-miR-222 suppresses caprine parainfluenza virus type 3 replication via downregulation of interferon regulatory factor 2. Vet Microbiol. 2018;224:58–65.PubMedCrossRef
30.
Ouyang W, Wang YS, Du XN, Liu HJ, Zhang HB. gga-miR-9* inhibits IFN production in antiviral innate immunity by targeting interferon regulatory factor 2 to promote IBDV replication. Vet Microbiol. 2015;178:41–9.PubMedCrossRef
31.
Mukherjee RM, Bansode B, Gangwal P, Jakkampudi A, Reddy PB, Rao PN, et al. Human interferon regulatory factor 2 gene expression is induced in chronic hepatitis C virus infection-a possible mode of viral persistence. J Clin Exp Hepatol. 2012;2:27–34.PubMedPubMedCentralCrossRef
32.
Nguyen H, Hiscott J, Pitha PM. The growing family of interferon regulatory factors. Cytokine Growth Factor Rev. 1997;8:293–312.PubMedCrossRef
33.
Ramana CV, Chatterjee-Kishore M, Nguyen H, Stark GR. Complex roles of Stat1 in regulating gene expression. Oncogene. 2000;19:2619–27.PubMedCrossRef
34.
Wang Y, Liu D, Chen P, Koeffler HP, Tong X, Xie D. Negative feedback regulation of IFN-gamma pathway by IFN regulatory factor 2 in esophageal cancers. Cancer Res. 2008;68:1136–43.PubMedCrossRef
35.
Ryan FJ, Carr JM, Furtado JM, Ma Y, Ashander LM, Simoes M, et al. Zika virus infection of human iris pigment epithelial cells. Front Immunol. 2021;12:644153.PubMedPubMedCentralCrossRef
36.
Mandal P, Krueger BE, Oldenburg D, Andry KA, Beard RS, White DW, et al. A gammaherpesvirus cooperates with interferon-alpha/beta-induced IRF2 to halt viral replication, control reactivation, and minimize host lethality. PLoS Pathog. 2011;7:e1002371.PubMedPubMedCentralCrossRef
37.
Yokota S, Okabayashi T, Yokosawa N, Fujii N. Growth arrest of epithelial cells during measles virus infection is caused by upregulation of interferon regulatory factor 1. J Virol. 2004;78:4591–8.PubMedPubMedCentralCrossRef
38.
Yokota S, Okabayashi T, Fujii N. Measles virus C protein suppresses gamma-activated factor formation and virus-induced cell growth arrest. Virology. 2011;414:74–82.PubMedCrossRef
39.
Choo A, Palladinetti P, Holmes T, Basu S, Shen S, Lock RB, et al. siRNA targeting the IRF2 transcription factor inhibits leukaemic cell growth. Int J Oncol. 2008;33:175–83.PubMed
40.
Kojima Y, Machida Y, Palani S, Caulfield TR, Radisky ES, Kaufmann SH, et al. FAM111A protects replication forks from protein obstacles via its trypsin-like domain. Nat Commun. 2020;11:1318.PubMedPubMedCentralCrossRef
41.
Metadata
Title
IRF2 inhibits ZIKV replication by promoting FAM111A expression to enhance the host restriction effect of RFC3
Authors
Kai Ren
Ya Zhu
Honggang Sun
Shilin Li
Xiaoqiong Duan
Shuang Li
Yujia Li
Bin Li
Limin Chen
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Virology Journal / Issue 1/2021
Electronic ISSN: 1743-422X
DOI
https://doi.org/10.1186/s12985-021-01724-8

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