Volume 25, Issue 3 (5-2021)                   IBJ 2021, 25(3): 169-179 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Shojaei Jeshvaghani Z, Soleimani M, Asgharpour S, Arefian E. Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway. IBJ 2021; 25 (3) :169-179
URL: http://ibj.pasteur.ac.ir/article-1-2925-en.html
Latency-Associated Transcript-Derived MicroRNAs in Herpes Simplex Virus Type 1 Target SMAD3 and SMAD4 in TGF-β/Smad Signaling Pathway
Zahra Shojaei Jeshvaghani , Masoud Soleimani , Sara Asgharpour , Ehsan Arefian *
Abstract:  
Background: During its latent infection, hepatic stellate cell (HSV-1) produces only a micro RNA (miRNA) precursor called latency-associated transcript (LAT), which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell signaling pathways that can be affected by HSV-1 is the TGF-β/Smad pathway. Herein, we investigated the potential role of the LAT as well as three LAT-derived miRNAs in targeting SMAD3 and SMAD4, as two main mediators in TGF-β/Smad. Methods: The selection of LAT-derived miRNAs was based on the search results obtained from an online miRNA prediction tool. HEK293T cells were transfected with each miRNA-expressing lentivector and with the construct-expressing LAT. To survey the effect of LAT on the expression of pro-fibrotic markers, we transfected LX-2 cells with LAT construct. The impact of viral miRNA overexpression on SMADs and fibrotic markers was measured by quantitative PCR and luciferase assays. Results: Among the LAT-derived miRNAs, miR-H2, miR-H3, and miR-H4 were selected for the study. Our results demonstrated that while miR-H2 binds to both SMAD mRNAs, miR-H3 and miR-H4 inhibit only the expression of the SMAD4 and SMAD3, respectively. Transfection of the LX-2 with LAT also decreased pro-fibrotic genes expression. Conclusion: Our findings display that LAT negatively regulates TGF-β/Smad through targeting SMAD3 and SMAD4 by its miRNAs. These viral miRNAs can also contribute to the development of therapeutic interventions in diseases for which prevention or treatment can be achieved through targeting TGF-β pathway.
Keywords: Herpesvirus 1, Latency associated transcript, microRNAs, SMAD3 protein, SMAD4 protein
Full-Text [PDF 1237 kb]      
Type of Study: Full Length/Original Article | Subject: Related Fields
References
1. Umbach JL, Cullen BR. The role of RNAi and microRNAs in animal virus replication and antiviral immunity. Genes and development 2009; 23(10): 1151-1164. [DOI:10.1101/gad.1793309]
2. Cullen BR. Viral and cellular messenger RNA targets of viral microRNAs. Nature 2009; 457(7228): 421-425. [DOI:10.1038/nature07757]
3. McGeoch DJ, Rixon FJ, Davison AJ. Topics in herpesvirus genomics and evolution. Virus research 2006; 117(1): 90-104 [DOI:10.1016/j.virusres.2006.01.002]
4. Bloom DC. HSV LAT and neuronal survival. International reviews of immunology 2004; 23(1-2): 187-198. [DOI:10.1080/08830180490265592]
5. Umbach JL, Kramer MF, Jurak I, Karnowski HW, Coen DM, Cullen BR. MicroRNAs expressed by herpes simplex virus 1 during latent infection regulate viral mRNAs. Nature 2008; 454(7205): 780-783. [DOI:10.1038/nature07103]
6. Umbach JL, Nagel MA, Cohrs RJ, Gilden DH, Cullen BR. Analysis of human alphaherpesvirus microRNA expression in latently infected human trigeminal ganglia. Journal of virology 2009; 83(20): 10677-10683. [DOI:10.1128/JVI.01185-09]
7. Jurak I, Kramer MF, Mellor JC, Van Lint AL, Roth FP, Knipe DM, Coen DM. Numerous conserved and divergent microRNAs expressed by herpes simplex viruses 1 and 2. Journal of virology 2010; 84(9): 4659-4672. [DOI:10.1128/JVI.02725-09]
8. Munson DJ, Burch AD. A novel miRNA produced during lytic HSV-1 infection is important for efficient replication in tissue culture. Archives of virology 2012; 157(9): 1677-1688. [DOI:10.1007/s00705-012-1345-4]
9. Wu W, Guo Z, Zhang X, Guo L, Liu L, Liao Y, Wang J, Wang L, Li Q. A microRNA encoded by HSV-1 inhibits a cellular transcriptional repressor of viral immediate early and early genes. Science China life sciences 2013; 56(4): 373-383. [DOI:10.1007/s11427-013-4458-4]
10. Han Z, Liu X, Chen X, Zhou X, Du T, Roizman B, Zhou G. miR-H28 and miR-H29 expressed late in productive infection are exported and restrict HSV-1 replication and spread in recipient cells. Proceedings of the national academy of sciences 2016; 113(7): E894-E901. [DOI:10.1073/pnas.1525674113]
11. Flores O, Nakayama S, Whisnant AW, Javanbakht H, Cullen BR, Bloom DC. Mutational inactivation of herpes simplex virus 1 microRNAs identifies viral mRNA targets and reveals phenotypic effects in culture. Journal of virology 2013; 87(12): 6589-6603. [DOI:10.1128/JVI.00504-13]
12. Everett RD. ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 2000; 22(8): 761-770. https://doi.org/10.1002/1521-1878(200008)22:8<761::AID-BIES10>3.0.CO;2-A [DOI:10.1002/1521-1878(200008)22:83.0.CO;2-A]
13. Preston C. Control of herpes simplex virus type 1 mRNA synthesis in cells infected with wild-type virus or the temperature-sensitive mutant tsK. Journal of virology 1979; 29(1): 275-284. [DOI:10.1128/JVI.29.1.275-284.1979]
14. Li Y, Zhang C, Chen X, Yu J, Wang Y, Yang Y, Du M, Jin H, Ma Y, He B, Cao Y. ICP34. 5 protein of herpes simplex virus facilitates the initiation of protein translation by bridging eukaryotic initiation factor 2α (eIF2α) and protein phosphatase 1. Journal of biological chemistry 2011; 286(28): 24785-24792. [DOI:10.1074/jbc.M111.232439]
15. Gupta A, Gartner J, Sethupathy P, Hatzigeorgiou A, Fraser N. Anti-apoptotic function of a microRNA encoded by the HSV-1 latency-associated transcript. Nature 2006; 442(7098): 82-85. [DOI:10.1038/nature04836]
16. Nie Y, Cui D, Pan Z, Deng J, Huang Q, Wu K. HSV-1 infection suppresses TGF-β1 and SMAD3 expression in human corneal epithelial cells. Molecular vision 2008; 14: 1631-1638.
17. Hu M, Dutt J, Arrunategui-Correa V, Baltatzis S, Foster CS. Cytokine mRNA in BALB/c mouse corneas infected with herpes simplex virus. Eye (Lond) 1999; 13(Pt 3a): 309-313. [DOI:10.1038/eye.1999.80]
18. Chen L, Yang T, Lu DW, Zhao H, Feng YL, Chen H, Chen DQ, Vaziri ND, Zhao YY. Central role of dysregulation of TGF-β/Smad in CKD progression and potential targets of its treatment. Biomedicine and Pharmacotherapy 2018; 101: 670-681. [DOI:10.1016/j.biopha.2018.02.090]
19. Eser PO, Jänne PA. TGFβ pathway inhibition in the treatment of non-small cell lung cancer,. Pharmacology and therapeutics 2018; 184: 112-130. [DOI:10.1016/j.pharmthera.2017.11.004]
20. Katz LH, Likhter M, Jogunoori W, Belkin M, Ohshiro K, Mishra L. TGF-β signaling in liver and gastrointestinal cancers. Cancer letters 2016; 379(2): 166-172. [DOI:10.1016/j.canlet.2016.03.033]
21. Xu L, Hui AY, Albanis E, Arthur MJ, O'Byrne SM, Blaner WS, Mukherjee P, Friedman S, Eng FJ. Human hepatic stellate cell lines, LX-1 and LX-2: new tools
22. for analysis of hepatic fibrosis. Gut 2005; 54(1): 142-151. [DOI:10.1136/gut.2004.042127]
23. Zhong YQ, Wei J, Fu YR, Shao J, Liang YW, Lin YH, Liu J, Zhu ZH. Toxicity of cationic liposome lipofectamine 2000 in human pancreatic cancer Capan-2 cells. Nan fang yi ke da xue xue bao 2008; 28(11): 1981-1984.
24. Shi Y, Wang YF, Jayaraman L, Yang H, Massagué J, Pavletich NP. Crystal structure of a Smad MH1 domain bound to DNA: insights on DNA binding in TGF-β signaling. Cell 1998; 94(5): 585-594. [DOI:10.1016/S0092-8674(00)81600-1]
25. Lee DK, Kim BC, Kim IY, ah Cho E, Satterwhite DJ, Kim SJ. The human papilloma virus E7 oncoprotein inhibits transforming growth factor-β signaling by blocking binding of the Smad complex to its target sequence. Journal of Biological Chemistry 2002; 277(41): 38557-38564. [DOI:10.1074/jbc.M206786200]
26. Seo T, Park J, Choe J. Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 1 inhibits transforming growth factor-β signaling. Cancer research 2005; 65(5): 1738-1747. [DOI:10.1158/0008-5472.CAN-04-2374]
27. Arnulf B, Villemain A, Nicot C, Mordelet E, Charneau P, Kersual J, Zermati Y, Mauviel A, Bazarbachi A, Hermine O. Human T-cell lymphotropic virus oncoprotein Tax represses TGF-β1 signaling in human T cells via c-Jun activation: a potential mechanism of
28. HTLV-I leukemogenesis. Blood 2002; 100(12): 4129-4138. [DOI:10.1182/blood-2001-12-0372]
29. Nicole Pavio, Battaglia S, Boucreux D, Arnulf B, Sobesky R, Hermine O, Brechot C. Hepatitis C virus core variants isolated from liver tumor but not from adjacent non-tumor tissue interact with Smad3 and inhibit the TGF-β pathway. Oncogene 2005; 24: 6119-6132. [DOI:10.1038/sj.onc.1208749]
30. Gottwein E, Cullen BR. Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell host and microbe 2008; 3(6): 375-387. [DOI:10.1016/j.chom.2008.05.002]
31. Györfi AH, Matei AE, Distler JH. Targeting TGF-β signaling for the treatment of fibrosis. Matrix biology 2018; 68-69: 8-27. [DOI:10.1016/j.matbio.2017.12.016]
32. Nakatsukasa H, Nagy P, Evarts RP, Hsia CC, Marsden E, Thorgeirsson SS. Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis. Journal of clinical investigation 1990; 85(6): 1833-1843. [DOI:10.1172/JCI114643]
33. Garber DA, Schaffer PA, Knipe DM. A LAT-associated function reduces productive-cycle gene expression during acute infection of murine sensory neurons with herpes simplex virus type 1. Journal of virology 1997; 71(8): 5885-5893. [DOI:10.1128/JVI.71.8.5885-5893.1997]
34. Perng GC, Jones J, Ciacci-Zanella J, Stone M, Henderson G, Yukht A, Slanina SM, Hofman FM, Ghiasi H, Nesburn AB, Wechster SL. Virus-induced neuronal apoptosis blocked by the herpes simplex virus latency-associated transcript. Science 2000; 287(5457): 1500-1503. [DOI:10.1126/science.287.5457.1500]
35. Cui C, Griffiths A, Li G, Silva LM, Kramer MF, Gaasterland T, Wang XJ, Coen DM. Prediction and identification of herpes simplex virus 1-encoded microRNAs. Journal of virology 2006; 80(11): 5499-5508. [DOI:10.1128/JVI.00200-06]
36. Liu X, Hu H, Yin JQ. Therapeutic strategies against TGF‐β signaling pathway in hepatic fibrosis. Liver International 2006; 26(1): 8-22. [DOI:10.1111/j.1478-3231.2005.01192.x]
Add your comments about this article : Your username or Email:
CAPTCHA
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

© 2024 CC BY-NC 4.0 | Iranian Biomedical Journal

Designed & Developed by : Yektaweb