Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Letter Article

The Antiviral Effects of Sodium Phenylbutyrate Against BoHV-1 Infection In Vitro

Author(s): Xinye Chen, Guoqiang Zhu* and Liqian Zhu*

Volume 16, Issue 12, 2019

Page: [1370 - 1377] Pages: 8

DOI: 10.2174/1570180816666190222155958

Price: $65

Abstract

Introduction: The alteration of histone acetylation is a known mechanism to regulate gene expression, and thereby affecting various cellular processes. Histone deacetylases (HDACs) are known to regulate histone acetylation by removal of the acetyl group from lysines. HDAC inhibitor such as Sodium Phenylbutyrate (PB) and Valproic Acid (VPA) have been reported to affect multiple virus infection while whether they affect BoHV-1 infection is unknown.

Objectives: The aim of the study is to investigate whether PB and VPA effects BoHV-1 infection and the virus induced inflammation related signaling including Erk1/2 and p38MAPK signaling.

Methods: To assess the antiviral effects of PB and VPA on BoHV-1 infection, MDBK cells were treated with these inhibitors at different concentrations. Then time addition was performed to pinpoint which stages of virus infection was affected by the chemicals. In order to assess whether PB affect viral gene expression, we detected the viral IE genes such as bICP0, bICP4 and bICP22 using real-time PCR assay. The effects of PB had on the activation of inflammation related signaling including Erk1/2 and p38MAPK in response to the virus infection were also detected.

Results: Here, for the first time we reveals that PB but not VPA affects BoHV-1 infection at late stages of infection. It affected the expression of IE genes such as bICP0, bICP4 and bICP22. Interestingly, PB enhanced the activation of both Erk1/2 and p38MAPK signaling stimulated by BoHV-1 infection.

Conclusion: HDAC inhibitor PB significantly inhibited BoHV-1 infection partially through the interruption of certain viral IE gene expression. Though PB has been reported to have antiinflammatory effects, we found that it enhanced the activation of inflammation pertinent signaling of both Erk1/2 and p38MAPK stimulated by BoHV-1 infection.

Keywords: BoHV-1, sodium phenylbutyrate, MAPK, inflammatory response, valproic acid, histone deacetylases.

« Previous Next »
Graphical Abstract

[1]
Tikoo, S.K.; Campos, M.; Babiuk, L.A. Bovine herpesvirus 1 (BHV-1): Biology, pathogenesis, and control. Adv. Virus Res., 1995, 45, 191-223.
[http://dx.doi.org/10.1016/S0065-3527(08)60061-5] [PMID: 7793325]
[2]
Hodgson, P.D.; Aich, P.; Manuja, A.; Hokamp, K.; Roche, F.M.; Brinkman, F.S.L.; Potter, A.; Babiuk, L.A.; Griebel, P.J. Effect of stress on viral-bacterial synergy in bovine respiratory disease: Novel mechanisms to regulate inflammation. Comp. Funct. Genomics, 2005, 6(4), 244-250.
[http://dx.doi.org/10.1002/cfg.474] [PMID: 18629190]
[3]
Jones, C.S.C. Bovine herpesvirus type 1 (BHV-1) is an important cofactor in the bovine respiratory disease complex.Veterinary Clinics of North America, Food Animal Practice, Bovine Respiratory Disease; Broderson, V.L.C.B., Ed.; Elsevier: New York, NY, 2010, Vol. 26, pp. 303-321.
[http://dx.doi.org/10.1016/j.cvfa.2010.04.007]
[4]
Yates, W.D.; Babiuk, L.A.; Jericho, K.W. Viral-bacterial pneumonia in calves: Duration of the interaction between bovine herpesvirus 1 and Pasteurella haemolytica. Can. J. Comp. Med., 1983, 47(3), 257-264.
[PMID: 6315196]
[5]
Neibergs, H.L.; Seabury, C.M.; Wojtowicz, A.J.; Wang, Z.; Scraggs, E.; Kiser, J.N.; Neupane, M.; Womack, J.E.; Van Eenennaam, A.; Hagevoort, G.R.; Lehenbauer, T.W.; Aly, S.; Davis, J.; Taylor, J.F. Susceptibility loci revealed for bovine respiratory disease complex in pre-weaned holstein calves. BMC Genomics, 2014, 15, 1164.
[http://dx.doi.org/10.1186/1471-2164-15-1164] [PMID: 25534905]
[6]
Fulton, R.W.; d’Offay, J.M.; Landis, C.; Miles, D.G.; Smith, R.A.; Saliki, J.T.; Ridpath, J.F.; Confer, A.W.; Neill, J.D.; Eberle, R.; Clement, T.J.; Chase, C.C.; Burge, L.J.; Payton, M.E. Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease. Vaccine, 2016, 34(30), 3478-3492.
[http://dx.doi.org/10.1016/j.vaccine.2016.04.020] [PMID: 27108192]
[7]
Jones, C.; Chowdhury, S. A review of the biology of bovine herpesvirus type 1 (BHV-1), its role as a cofactor in the bovine respiratory disease complex and development of improved vaccines. Anim. Health Res. Rev., 2007, 8(2), 187-205.
[http://dx.doi.org/10.1017/S146625230700134X] [PMID: 18218160]
[8]
Newcomer, B.W.; Cofield, L.G.; Walz, P.H.; Givens, M.D. Prevention of abortion in cattle following vaccination against bovine herpesvirus 1: A meta-analysis. Prev. Vet. Med., 2017, 138, 1-8.
[http://dx.doi.org/10.1016/j.prevetmed.2017.01.005] [PMID: 28237224]
[9]
Fulton, R.W.; d’Offay, J.M.; Eberle, R.; Moeller, R.B.; Campen, H.V.; O’Toole, D.; Chase, C.; Miller, M.M.; Sprowls, R.; Nydam, D.V. Bovine herpesvirus-1: Evaluation of genetic diversity of subtypes derived from field strains of varied clinical syndromes and their relationship to vaccine strains. Vaccine, 2015, 33(4), 549-558.
[http://dx.doi.org/10.1016/j.vaccine.2014.11.033] [PMID: 25454086]
[10]
West, A.C.; Mattarollo, S.R.; Shortt, J.; Cluse, L.A.; Christiansen, A.J.; Smyth, M.J.; Johnstone, R.W. An intact immune system is required for the anticancer activities of histone deacetylase inhibitors. Cancer Res., 2013, 73(24), 7265-7276.
[http://dx.doi.org/10.1158/0008-5472.CAN-13-0890] [PMID: 24158093]
[11]
Peña-Quintana, L.; Llarena, M.; Reyes-Suárez, D.; Aldámiz-Echevarria, L. Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: Patient perspectives. Patient Prefer. Adherence, 2017, 11, 1489-1496.
[http://dx.doi.org/10.2147/PPA.S136754] [PMID: 28919721]
[12]
Bolden, J.E.; Peart, M.J.; Johnstone, R.W. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov., 2006, 5(9), 769-784.
[http://dx.doi.org/10.1038/nrd2133] [PMID: 16955068]
[13]
Gediya, L.K.; Khandelwal, A.; Patel, J.; Belosay, A.; Sabnis, G.; Mehta, J.; Purushottamachar, P.; Njar, V.C. Design, synthesis, and evaluation of novel mutual prodrugs (hybrid drugs) of all-trans-retinoic acid and histone deacetylase inhibitors with enhanced anticancer activities in breast and prostate cancer cells in vitro. J. Med. Chem., 2008, 51(13), 3895-3904.
[http://dx.doi.org/10.1021/jm8001839] [PMID: 18543902]
[14]
Valente, S.; Trisciuoglio, D.; De Luca, T.; Nebbioso, A.; Labella, D.; Lenoci, A.; Bigogno, C.; Dondio, G.; Miceli, M.; Brosch, G.; Del Bufalo, D.; Altucci, L.; Mai, A. 1,3,4-Oxadiazole-containing histone deacetylase inhibitors: Anticancer activities in cancer cells. J. Med. Chem., 2014, 57(14), 6259-6265.
[http://dx.doi.org/10.1021/jm500303u] [PMID: 24972008]
[15]
Göttlicher, M.; Minucci, S.; Zhu, P.; Krämer, O.H.; Schimpf, A.; Giavara, S.; Sleeman, J.P.; Lo Coco, F.; Nervi, C.; Pelicci, P.G.; Heinzel, T. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J., 2001, 20(24), 6969-6978.
[http://dx.doi.org/10.1093/emboj/20.24.6969] [PMID: 11742974]
[16]
Yang, J.; Deng, W.; Hau, P.M.; Liu, J.; Lau, V.M.; Cheung, A.L.; Huen, M.S.; Tsao, S.W. Epstein-Barr virus BZLF1 protein impairs accumulation of host DNA damage proteins at damage sites in response to DNA damage. Lab. Invest., 2015, 95(8), 937-950.
[http://dx.doi.org/10.1038/labinvest.2015.69] [PMID: 26006018]
[17]
Danaher, R.J.; Jacob, R.J.; Steiner, M.R.; Allen, W.R.; Hill, J.M.; Miller, C.S. Histone deacetylase inhibitors induce reactivation of herpes simplex virus type 1 in a latency-associated transcript-independent manner in neuronal cells. J. Neurovirol., 2005, 11(3), 306-317.
[http://dx.doi.org/10.1080/13550280590952817] [PMID: 16036811]
[18]
Archin, N.M.; Liberty, A.L.; Kashuba, A.D.; Choudhary, S.K.; Kuruc, J.D.; Crooks, A.M.; Parker, D.C.; Anderson, E.M.; Kearney, M.F.; Strain, M.C.; Richman, D.D.; Hudgens, M.G.; Bosch, R.J.; Coffin, J.M.; Eron, J.J.; Hazuda, D.J.; Margolis, D.M. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature, 2012, 487(7408), 482-485.
[http://dx.doi.org/10.1038/nature11286] [PMID: 22837004]
[19]
Crosby, B.; Deas, C.M. Repurposing medications for use in treating HIV infection: A focus on valproic acid as a latency-reversing agent. J. Clin. Pharm. Ther., 2018, 43(5), 740-745.
[http://dx.doi.org/10.1111/jcpt.12726] [PMID: 29959785]
[20]
Yang, X.; Zhu, X.; Ji, H.; Deng, J.; Lu, P.; Jiang, Z.; Li, X.; Wang, Y.; Wang, C.; Zhao, J.; Wang, Y.; Zhong, Y.; Yang, H.; Zhu, H. Quercetin synergistically reactivates human immunodeficiency virus type 1 latency by activating nuclear factorκB. Mol. Med. Rep., 2018, 17(2), 2501-2508.
[PMID: 29207194]
[21]
Delgado, F.G.; Cárdenas, P.; Castellanos, J.E. Valproic acid downregulates cytokine expression in human macrophages infected with dengue virus. Diseases, 2018, 6(3)E59
[http://dx.doi.org/10.3390/diseases6030059] [PMID: 29986388]
[22]
Frouco, G.; Freitas, F.B.; Martins, C.; Ferreira, F. Sodium phenylbutyrate abrogates African swine fever virus replication by disrupting the virus-induced hypoacetylation status of histone H3K9/K14. Virus Res., 2017, 242, 24-29.
[http://dx.doi.org/10.1016/j.virusres.2017.09.009] [PMID: 28916365]
[23]
Vázquez-Calvo, A.; Saiz, J.C.; Sobrino, F.; Martín-Acebes, M.A. Inhibition of enveloped virus infection of cultured cells by valproic acid. J. Virol., 2011, 85(3), 1267-1274.
[http://dx.doi.org/10.1128/JVI.01717-10] [PMID: 21106740]
[24]
Zhu, L.; Ding, X.; Zhu, X.; Meng, S.; Wang, J.; Zhou, H.; Duan, Q.; Tao, J.; Schifferli, D.M.; Zhu, G. Biphasic activation of PI3K/Akt and MAPK/Erk1/2 signaling pathways in bovine herpesvirus type 1 infection of MDBK cells. Vet. Res. (Faisalabad), 2011, 42, 57.
[http://dx.doi.org/10.1186/1297-9716-42-57] [PMID: 21492439]
[25]
Hazzalin, C.A.; Mahadevan, L.C. MAPK-regulated transcription: A continuously variable gene switch? Nat. Rev. Mol. Cell Biol., 2002, 3(1), 30-40.
[http://dx.doi.org/10.1038/nrm715] [PMID: 11823796]
[26]
Passos, G.F.; Medeiros, R.; Marcon, R.; Nascimento, A.F.; Calixto, J.B.; Pianowski, L.F. The role of PKC/ERK1/2 signaling in the anti-inflammatory effect of tetracyclic triterpene euphol on TPA-induced skin inflammation in mice. Eur. J. Pharmacol., 2013, 698(1-3), 413-420.
[http://dx.doi.org/10.1016/j.ejphar.2012.10.019] [PMID: 23099255]
[27]
Herlaar, E.; Brown, Z. p38 MAPK signalling cascades in inflammatory disease. Mol. Med. Today, 1999, 5(10), 439-447.
[http://dx.doi.org/10.1016/S1357-4310(99)01544-0] [PMID: 10498912]
[28]
Hu, S.; Sheng, W.S.; Schachtele, S.J.; Lokensgard, J.R. Reactive oxygen species drive herpes simplex virus (HSV)-1-induced proinflammatory cytokine production by murine microglia. J. Neuroinflammation, 2011, 8, 123.
[http://dx.doi.org/10.1186/1742-2094-8-123] [PMID: 21943001]
[29]
Zhu, L.; Yuan, C.; Huang, L.; Ding, X.; Wang, J.; Zhang, D.; Zhu, G. The activation of p38MAPK and JNK pathways in bovine herpesvirus 1 infected MDBK cells. Vet. Res., 2016, 47(1), 91.
[http://dx.doi.org/10.1186/s13567-016-0377-2] [PMID: 27590675]
[30]
Roy, A.; Ghosh, A.; Jana, A.; Liu, X.; Brahmachari, S.; Gendelman, H.E.; Pahan, K. Sodium phenylbutyrate controls neuroinflammatory and antioxidant activities and protects dopaminergic neurons in mouse models of Parkinson’s disease. PLoS One, 2012, 7(6)e38113
[http://dx.doi.org/10.1371/journal.pone.0038113] [PMID: 22723850]
[31]
Zhu, L.; Jiang, X.; Fu, X.; Qi, Y.; Zhu, G. The involvement of histone H3 acetylation in bovine herpesvirus 1 replication in MDBK cells. Viruses, 2018, 10(10)E525
[http://dx.doi.org/10.3390/v10100525] [PMID: 30261679]
[32]
Michaelis, M.; Suhan, T.; Reinisch, A.; Reisenauer, A.; Fleckenstein, C.; Eikel, D.; Gümbel, H.; Doerr, H.W.; Nau, H.; Cinatl, J., Jr Increased replication of human cytomegalovirus in retinal pigment epithelial cells by valproic acid depends on histone deacetylase inhibition. Invest. Ophthalmol. Vis. Sci., 2005, 46(9), 3451-3457.
[http://dx.doi.org/10.1167/iovs.05-0369] [PMID: 16123451]
[33]
Roque, T.; Boncoeur, E.; Saint-Criq, V.; Bonvin, E.; Clement, A.; Tabary, O.; Jacquot, J. Proinflammatory effect of sodium 4-phenylbutyrate in deltaF508-cystic fibrosis transmembrane conductance regulator lung epithelial cells: Involvement of extracellular signal-regulated protein kinase 1/2 and c-Jun-NH2-terminal kinase signaling. J. Pharmacol. Exp. Ther., 2008, 326(3), 949-956.
[http://dx.doi.org/10.1124/jpet.107.135186] [PMID: 18574003]
[34]
Zhang, X.; Wei, L.; Yang, Y.; Yu, Q. Sodium 4-phenylbutyrate induces apoptosis of human lung carcinoma cells through activating JNK pathway. J. Cell. Biochem., 2004, 93(4), 819-829.
[http://dx.doi.org/10.1002/jcb.20173] [PMID: 15389886]
[35]
Zhu, L.; Jones, C. The high mobility group AT-hook 1 protein stimulates bovine herpesvirus 1 productive infection. Virus Res., 2017, 238, 236-242.
[http://dx.doi.org/10.1016/j.virusres.2017.07.002] [PMID: 28684158]

Rights & Permissions Print Cite
Article Metrics
27
2
1
© 2024 Bentham Science Publishers | Privacy Policy