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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

In Vitro Anti-Viral Effects of Small Heat Shock Proteins 20 and 27: A Novel Therapeutic Approach

Author(s): Rouhollah Vahabpour, Sepehr Soleymani, Farzin Roohvand, Rezvan Zabihollahi and Azam Bolhassani*

Volume 20, Issue 12, 2019

Page: [1011 - 1017] Pages: 7

DOI: 10.2174/1389201020666190729104648

Price: $65

Abstract

Background: The protective effects of heat shock proteins (Hsps) were studied in some infectious and non-infectious diseases, but their specificity was slightly known in various disorders. Among Hsps, small Hsps (e.g. Hsp27 and Hsp20) have important roles in protein folding and translocation, and also in immunity.

Methods: In this study, overexpression of Hsp20 and Hsp27 was performed by transfection of the plasmids encoding Hsp20 and Hsp27 (pEGFP-Hsp20 and pEGFP-Hsp27) into Huh7.5, Hela and Vero cells using Lipofectamine along with heat shock. Then, their anti-herpes simplex virus-1 (HSV-1), anti- human immunodeficiency virus-1 (HIV-1) and anti-hepatitis C virus (HCV) effects, as well as cytotoxicity, were evaluated in vitro, for the first time.

Results: Our data showed that simultaneous treatment with Lipofectamine and heat shock augmented the rate of transfection and subsequently the expression of Hsps in these cells. Moreover, overexpression of Hsp20 in HCV-infected Huh7.5 cells, HIV-infected Hela cells and HSV-infected Vero cells reduced the replication of HCV, HIV and HSV, respectively. In contrast, overexpression of Hsp27 significantly decreased HSV replication similar to Hsp20, but it did not affect the replication of HIV and HCV.

Conclusion: Generally, Hsp20 was identified as a novel anti-HCV, anti-HSV and anti-HIV agent, but Hsp27 was efficient in the suppression of HSV infection. These Hsps may act through suppression of virus entry and/ or through interaction with viral proteins. Thus, it is necessary to determine their exact mechanisms in the near future.

Keywords: HCV, HIV, HSV, small Hsp, transfection, anti-viral effect.

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[1]
Arrigo, A.P. Human small heat shock proteins: Protein interactomes of homo- and hetero-oligomeric complexes: An update. FEBS Lett., 2013, 587(13), 1959-1969.
[http://dx.doi.org/10.1016/j.febslet.2013.05.011] [PMID: 23684648]
[2]
Kappé, G.; Franck, E.; Verschuure, P.; Boelens, W.C.; Leunissen, J.A.; de Jong, W.W. The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones, 2003, 8(1), 53-61.
[http://dx.doi.org/10.1379/1466-1268(2003)8<53:THGECS>2.0.CO;2] [PMID: 12820654]
[3]
de Jong, W.W.; Leunissen, J.A.; Voorter, C.E. Evolution of the alpha-crystallin/small heat-shock protein family. Mol. Biol. Evol., 1993, 10(1), 103-126.
[PMID: 8450753]
[4]
Takemoto, L.; Emmons, T.; Horwitz, J. The C-terminal region of α-crystallin: Involvement in protection against heat-induced denaturation. Biochem. J., 1993, 294(Pt 2), 435-438.
[http://dx.doi.org/10.1042/bj2940435] [PMID: 8373358]
[5]
Pasta, S.Y.; Raman, B.; Ramakrishna, T.; Rao, ChM. The IXI/V motif in the C-terminal extension of alpha-crystallins: Alternative interactions and oligomeric assemblies. Mol. Vis., 2004, 10, 655-662.
[PMID: 15448619]
[6]
Sudnitsyna, M.V.; Mymrikov, E.V.; Seit-Nebi, A.S.; Gusev, N.B. The role of intrinsically disordered regions in the structure and functioning of small heat shock proteins. Curr. Protein Pept. Sci., 2012, 13(1), 76-85.
[http://dx.doi.org/10.2174/138920312799277875] [PMID: 22044147]
[7]
Horwitz, J.; Huang, Q.L.; Ding, L.L. Alpha-crystallin can function as a molecular chaperone. Proc. Natl. Acad. Sci. USA, 1992, 89(21), 10449-10453.
[http://dx.doi.org/10.1073/pnas.89.21.10449] [PMID: 1438232]
[8]
Arrigo, A.P. In search of the molecular mechanism by which small stress proteins counteract apoptosis during cellular differentiation. J. Cell. Biochem., 2005, 94(2), 241-246.
[http://dx.doi.org/10.1002/jcb.20349] [PMID: 15546148]
[9]
Arrigo, A.P.; Simon, S. Dual, beneficial and deleterous, roles of small stress proteins in human diseases: Implications for therapeutic strategies in: Small stress proteins in human diseases. Nova Sci., 2010, 457-476.
[10]
Mymrikov, E.V.; Seit-Nebi, A.S.; Gusev, N.B. Large potentials of small heat shock proteins. Physiol. Rev., 2011, 91(4), 1123-1159.
[http://dx.doi.org/10.1152/physrev.00023.2010] [PMID: 22013208]
[11]
Wang, X.; Chen, M.; Zhou, J.; Zhang, X. HSP27, 70 and 90, anti-apoptotic proteins, in clinical cancer therapy (Review) Int. J. Oncol., 2014, 45(1), 18-30.
[http://dx.doi.org/10.3892/ijo.2014.2399] [PMID: 24789222]
[12]
Bakthisaran, R.; Tangirala, R.; Rao, ChM. Small heat shock proteins: Role in cellular functions and pathology. Biochim. Biophys. Acta, 2015, 1854(4), 291-319.
[http://dx.doi.org/10.1016/j.bbapap.2014.12.019] [PMID: 25556000]
[13]
Noda, T.; Kumada, T.; Takai, S.; Matsushima-Nishiwaki, R.; Yoshimi, N.; Yasuda, E.; Kato, K.; Toyoda, H.; Kaneoka, Y.; Yamaguchi, A.; Kozawa, O. Expression levels of heat shock protein 20 decrease in parallel with tumor progression in patients with hepatocellular carcinoma. Oncol. Rep., 2007, 17(6), 1309-1314.
[http://dx.doi.org/10.3892/or.17.6.1309] [PMID: 17487383]
[14]
Thrift, A.P.; El-Serag, H.B.; Kanwal, F. Global epidemiology and burden of HCV infection and HCV-related disease. Nat. Rev. Gastroenterol. Hepatol., 2017, 14(2), 122-132.
[http://dx.doi.org/10.1038/nrgastro.2016.176] [PMID: 27924080]
[15]
Li, J.R.; Li, W.J.; Cheng, J.J.; Huang, M.H.; Wu, Z.Y.; Jiang, C.C. A Simple but accurate method for evaluating drug-resistance in infectious HCVcc system. In: Hindawi BioMedical Research International; , 2017 ; pp. 1-9..
[16]
Imran, M.; Waheed, Y.; Ghazal, A.; Ullah, S.; Safi, S.Z.; Jamal, M.; Ali, M.; Atif, M.; Imran, M.; Ullah, F. Modern biotechnology-based therapeutic approaches against HIV infection. Biomed. Rep., 2017, 7(6), 504-507.
[http://dx.doi.org/10.3892/br.2017.1006] [PMID: 29250325]
[17]
Chattopadhyay, D.; Sarkar, M.C.; Chatterjee, T.; Sharma Dey, R.; Bag, P.; Chakraborti, S.; Khan, M.T. Recent advancements for the evaluation of anti-viral activities of natural products. N. Biotechnol., 2009, 25(5), 347-368.
[http://dx.doi.org/10.1016/j.nbt.2009.03.007] [PMID: 19464980]
[18]
Yu, X.; He, S. The interplay between human herpes simplex virus infection and the apoptosis and necroptosis cell death pathways. Virol. J., 2016, 13, 77.
[http://dx.doi.org/10.1186/s12985-016-0528-0] [PMID: 27154074]
[19]
Pipes, B.L.; Vasanwala, F.H.; Tsang, T.C.; Zhang, T.; Luo, P.; Harris, D.T. Brief heat shock increases stable integration of lipid-mediated DNA transfections. Biotechniques, 2005, 38(1), 48-52, 50, 52.
[http://dx.doi.org/10.2144/05381BM05] [PMID: 15679084]
[20]
Braga, A.C.S.; Carneiro, B.M.; Batista, M.N.; Akinaga, M.M.; Bittar, C.; Rahal, P. Heat shock proteins HSPB8 and DNAJC5B have HCV antiviral activity. PLoS One, 2017, 12(11)e0188467
[http://dx.doi.org/10.1371/journal.pone.0188467] [PMID: 29182667]
[21]
Zabihollahi, R.; Sadat, S.M.; Vahabpour, R.; Aghasadeghi, M.R.; Memarnejadian, A.; Ghazanfari, T.; Salehi, M.; Rezaei, A.; Azadmanesh, K. Development of single-cycle replicable human immunodeficiency virus 1 mutants. Acta Virol., 2011, 55(1), 15-22.
[http://dx.doi.org/10.4149/av_2011_01_15] [PMID: 21434701]
[22]
Zabihollahi, R.; Motevaseli, E.; Sadat, S.M.; Azizi-Saraji, A.R.; Asaadi-Dalaie, S.; Modarressi, M.H. Inhibition of HIV and HSV infection by vaginal lactobacilli in vitro and in vivo. Daru, 2012, 20(1), 53.
[http://dx.doi.org/10.1186/2008-2231-20-53] [PMID: 23351891]
[23]
Wakita, T.; Pietschmann, T.; Kato, T.; Date, T.; Miyamoto, M.; Zhao, Z.; Murthy, K.; Habermann, A.; Kräusslich, H.G.; Mizokami, M.; Bartenschlager, R.; Liang, T.J. Production of infectious hepatitis C virus in tissue culture from a cloned viral genome. Nat. Med., 2005, 11(7), 791-796.
[http://dx.doi.org/10.1038/nm1268] [PMID: 15951748]
[24]
Liu, J.; Bai, J.; Zhang, L.; Jiang, Z.; Wang, X.; Li, Y.; Jiang, P. Hsp70 positively regulates porcine circovirus type 2 replication in vitro. Virology, 2013, 447(1-2), 52-62.
[http://dx.doi.org/10.1016/j.virol.2013.08.025] [PMID: 24210099]
[25]
Sedger, L.; Ramshaw, I.; Condie, A.; Medveczky, J.; Braithwaite, A.; Ruby, J. Vaccinia virus replication is independent of cellular HSP72 expression which is induced during virus infection. Virology, 1996, 225(2), 423-427.
[http://dx.doi.org/10.1006/viro.1996.0619] [PMID: 8918931]
[26]
Kim, M.Y.; Oglesbee, M. Virus-heat shock protein interaction and a novel axis for innate antiviral immunity. Cells, 2012, 1(3), 646-666.
[http://dx.doi.org/10.3390/cells1030646] [PMID: 24710494]
[27]
Conti, C.; De Marco, A.; Mastromarino, P.; Tomao, P.; Santoro, M.G. Antiviral effect of hyperthermic treatment in rhinovirus infection. Antimicrob. Agents Chemother., 1999, 43(4), 822-829.
[http://dx.doi.org/10.1128/AAC.43.4.822] [PMID: 10103186]
[28]
Li, G.; Zhang, J.; Tong, X.; Liu, W.; Ye, X. Heat shock protein 70 inhibits the activity of Influenza A virus ribonucleoprotein and blocks the replication of virus in vitro and in vivo. PLoS One, 2011, 6(2)e16546
[http://dx.doi.org/10.1371/journal.pone.0016546] [PMID: 21390211]
[29]
Haviv, Y.S.; Blackwell, J.L.; Li, H.; Wang, M.; Lei, X.; Curiel, D.T. Heat shock and heat shock protein 70i enhance the oncolytic effect of replicative adenovirus. Cancer Res., 2001, 61(23), 8361-8365.
[PMID: 11731408]
[30]
Takizaki, M.; Muranaka, S.; Haine, A.T.; Tokunaga, S.; Morimura, S.; Niidome, T. Enhancing mechanism of gene transfection by heat shock. Chem. Lett., 2017, 46(8), 1-8.
[http://dx.doi.org/10.1246/cl.170439]
[31]
Takai, T.; Ohmori, H. Enhancement of DNA transfection efficiency by heat treatment of cultured mammalian cells. Biochim. Biophys. Acta, 1992, 1129(2), 161-165.
[http://dx.doi.org/10.1016/0167-4781(92)90481-E] [PMID: 1730054]
[32]
Yu, L.; Ye, L.; Zhao, R.; Liu, Y.F.; Yang, S.J. HSP70 induced by Hantavirus infection interacts with viral nucleocapsid protein and its overexpression suppresses virus infection in Vero E6 cells. Am. J. Transl. Res., 2009, 1(4), 367-380.
[PMID: 19956449]
[33]
Amici, C.; Giorgi, C.; Rossi, A.; Santoro, M.G. Selective inhibition of virus protein synthesis by prostaglandin A1: A translational block associated with HSP70 synthesis. J. Virol., 1994, 68(11), 6890-6899.
[PMID: 7933069]
[34]
Oglesbee, M.J.; Liu, Z.; Kenney, H.; Brooks, C.L. The highly inducible member of the 70 kDa family of heat shock proteins increases canine distemper virus polymerase activity. J. Gen. Virol., 1996, 77(Pt 9), 2125-2135.
[http://dx.doi.org/10.1099/0022-1317-77-9-2125] [PMID: 8811012]
[35]
Bluhm, W.F.; Martin, J.L.; Mestril, R.; Dillmann, W.H. Specific heat shock proteins protect microtubules during simulated ischemia in cardiac myocytes. Am. J. Physiol., 1998, 275(6), H2243-H2249.
[http://dx.doi.org/10.1152/ajpheart.1998.275.6.H2243]
[36]
Liang, D.; Benko, Z.; Agbottah, E.; Bukrinsky, M.; Zhao, R.Y. Anti-VPR activities of heat shock protein 27. Mol. Med., 2007, 13(5-6), 229-239.
[http://dx.doi.org/10.2119/2007-00004.Liang] [PMID: 17622316]
[37]
Khachatoorian, R.; Ganapathy, E.; Ahmadieh, Y.; Wheatley, N.; Sundberg, C.; Jung, C.L.; Arumugaswami, V.; Raychaudhuri, S.; Dasgupta, A.; French, S.W. The NS5A-binding heat shock proteins HSC70 and HSP70 play distinct roles in the hepatitis C viral life cycle. Virology, 2014, 454-455, 118-127.
[http://dx.doi.org/10.1016/j.virol.2014.02.016] [PMID: 24725938]
[38]
Parent, R.; Qu, X.; Petit, M.A.; Beretta, L. The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity. Hepatology, 2009, 49(6), 1798-1809.
[http://dx.doi.org/10.1002/hep.22852] [PMID: 19434724]
[39]
Li, G.; Bukrinsky, M.; Zhao, R.Y. HIV-1 viral protein R (Vpr) and its interactions with host cell. Curr. HIV Res., 2009, 7(2), 178-183.
[http://dx.doi.org/10.2174/157016209787581436] [PMID: 19275587]

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