Inhibition of herpes simplex virus type 1 replication by novel hsa-miR-7704 in vitro

Mehdi Shabani , Bahram Nasr Esfahani, Bahar Sadegh Ehdaei, Sharareh Moghim , Arezoo Mirzaei, Mohammadreza Sharifi, Leili Mouhebat

Abstract


Herpes simplex virus type 1 (HSV-1) infections are one of the most common diseases in human population. HSV-1 causes subclinical, mild to severe diseases, especially in immunocompromised patients. Acyclovir has been used to reduce manifestations of HSV-1 infections. The extensive use of this drug has led to the development of resistant strains. Thus, designing a novel anti-herpes drug with different mechanisms of action is urgently needed. Cellular microRNAs (miRNAs) have direct antiviral effects in addition to their regulatory functions. In this study we used a novel miRNA (hsa-miR-7704), expressed in macrophages, to inhibit HSV-1 lytic infection in HeLa cells. Synthesized hsa-miR-7704 mimics were transfected into HSV-1 infected HeLa cell. The inhibitory effects of the miRNA were evaluated by plaque assay, real time polymerase chain reaction and the viral titers were measured by the 50% tissue culture infective dose (TCID50). The viral titer and cell cytopathic effect were dramatically decreased in HeLa cells transfected with hsa-miR-7704 (50 and 100 nM), compared with HSV-1 infected cells alone or transfected with the mock miRNA control. These results suggest that hsa-miR-7704 inhibits HSV-1 replication efficiently in vitro. This may provide an alternative mechanism to prevent HSV-1 infections.


Keywords


Antiviral therapy; HSV-1; Micro RNA; miR-has-7704; miR-SX1.

Full Text:

PDF

References


Taylor TJ, Brockman MA, McNamee EE, Knipe DM. Herpes simplex virus. Front Biosci. 2002;7:752-764.

Rabenau HF, Buxbaum S, Preiser W, Weber B, Doerr HW. Seroprevalence of herpes simplex virus types 1 and type 2 in the Frankfurt am Main area, Germany. Med Microbiol Immunol. 2002;190(4):153-160.

Xu F, Sternberg MR, Kottiri BJ, McQuillan GM, Lee FK, Nahmias AJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296(8):964-973.

Griffiths PD. Herpesviruses. Medicine. 2014; 42(1):34-38.

Sili U, Kaya A, Mert A, HSV Encephalitis Study Group. Herpes simplex virus encephalitis: clinical manifestations, diagnosis and outcome in 106 adult patients. J Clin Virol. 2014;60(2):112-118.

Vissani MA, Thiry E, Dal Pozzo F, Barrandeguy M. Antiviral agents against equid alphaherpesviruses: Current status and perspectives. Vet J. 2016;207: 38-44.

Farooq AV, Shukla D. Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol .2012;57(5):448-462.

Lam NN, Weir MA, Yao Z, Blake PG, Beyea MM, Gomes T, et al. Risk of acute kidney injury from oral acyclovir: a population-based study. Am J Kidney Dis. 2013;61(5):723-729.

Skalsky RL, Cullen BR. Viruses, microRNAs, and host interactions. Annu Rev Microbiol. 2010;64:123-141.

Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H. Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antivir Res. 2010;88(2):169-175.

Murakami Y, Aly HH, Tajima A, Inoue I, Shimotohno K. Regulation of the hepatitis C virus genome replication by miR-199a. J Hepatol. 2009;50(3):453-460.

Heikkilä O, Nygårdas M, Paavilainen H, Ryödi E, Hukkanen V. Interleukin-27 inhibits herpes simplex virus type 1 infection by activating STAT1 and 3, interleukin-6, and chemokines IP-10 and MIG. J Interferon Cytokine Res. 2016;36(11):617-629.

Swaminathan S, Hu X, Zheng X, Kriga Y, Shetty J, Zhao Y, et al. Interleukin-27 treated human macrophages induce the expression of novel microRNAs which may mediate anti-viral properties. Biochem Biophys Res Commun .2013;434(2):228-234.

Jin HY, Gonzalez-Martin A, Miletic AV, Lai M, Knight S, Sabouri-Ghomi M, et al. Transfection of microRNA mimics should be used with caution. Front Genet. 2015;6:340-362.

Li C, Zamore PD. Inhibiting miRNA function by antisense oligonucleotides in cultured mammalian cells. Cold Spring Harb Protoc. DOI: 10.1101/pdb.prot097535.

Martin C, Leyton L, Hott M, Arancibia Y, Spichiger C, McNiven MA, et al. Herpes simplex virus type 1 neuronal infection perturbs golgi apparatus integrity through activation of Src tyrosine kinase and Dyn-2 GTPase. Front Cell Infect Microbiol. 2017;7: 371-384.

van Meerloo J, Kaspers GJ, Cloos J. Cell sensitivity assays: the MTT assay. Methods Mol Biol. 2011;731:237-245.

Duan F, Ni S, Nie Y, Huang Q, Wu K. Small interfering RNA targeting for infected‐cell polypeptide 4 inhibits herpes simplex virus type 1 replication in retinal pigment epithelial cells. Clin Exp Ophthalmol .2012;40(2):195-204.

Köchl S, Niederstätter H, Parson W. DNA extraction and quantitation of forensic samples using the phenol-chloroform method and real-time PCR. Methods Mol Biol. 2005;297:13-30.

Jin F, Li S, Zheng K, Zhuo C, Ma K, Chen M, et al. Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach. PloS One. 2014;9(5):e96623.

Harbecke R, Oxman MN, Arnold BA, Ip C, Johnson GR, Levin MJ, et al. A real‐time PCR assay to identify and discriminate among wild‐type and vaccine strains of varicella‐zoster virus and herpes simplex virus in clinical specimens, and comparison with the clinical diagnoses. J Med Virol. 2009;81(7):1310-1322.

Stránská R, van Loon AM, Polman M, Schuurman R. Application of real-time PCR for determination of antiviral drug susceptibility of herpes simplex virus. Antimicrob Agents Chemother. 2002;46(9):2943-2947.

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.

Ma K, Jin F, Wang Q, Ren Z, Zheng K, Wang Y. siRNAs Targeting viral protein 5: the major capsid protein of herpes simplex virus-1 affects its propagation and cytoskeleton. Trop J Pharm Res. 2015;14(3):391-397.

Duan F, Liao J, Huang Q, Nie Y, Wu K. HSV-1 miR-H6 inhibits HSV-1 replication and IL-6 expression in human corneal epithelial cells in vitro. Clin Dev Immunol.2012;2012. Article ID: 192791

Poudyal D, Herman A, Adelsberger JW, Yang J, Hu X, Chen Q, et al. A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression. Sci Rep. 2018;8(1):900-912.


Refbacks

  • There are currently no refbacks.


Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.