Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway
Abstract
1. Introduction
2. Why Cell Penetrating Peptides Are of Particular Interest for Delivery of Bioactive Molecules
3. Antiviral Activity of Cell Penetrating Peptides Altering Hepadnaviral Replication
4. Anti-Duck Hepatitis B Virus Effect of Peptide Nucleic Acids coupled to Cell Penetrating Peptides Conjugates
5. Sugar Modified CPP-PNA Uptake and Their Anti-HBV Activity in HepaRG Cells
6. Antiviral Activity of CPP-Based Approaches against Other Viruses
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Trépo, C.; Chan, H.L.; Lok, A. Hepatitis B virus infection. Lancet 2014, 384, 2053–2063. [Google Scholar] [CrossRef]
- Zoulim, F.; Locarnini, S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology 2009, 137, 1593–1608.e2. [Google Scholar] [CrossRef] [PubMed]
- Scaglione, S.J.; Lok, A.S. Effectiveness of hepatitis B treatment in clinical practice. Gastroenterology 2012, 142, 1360–1368.e1. [Google Scholar] [CrossRef] [PubMed]
- Nielsen, P.E.; Egholm, M.; Berg, R.H.; Buchardt, O. Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide. Science 1991, 254, 1497–1500. [Google Scholar] [CrossRef] [PubMed]
- Egholm, M.; Buchardt, O.; Christensen, L.; Behrens, C.; Freier, S.M.; Driver, D.A.; Berg, R.H.; Kim, S.K.; Norden, B.; Nielsen, P.E. PNA hybridizes to complementary oligonucleotides obeying the Watson-Crick hydrogen-bonding rules. Nature 1993, 365, 566–568. [Google Scholar] [CrossRef] [PubMed]
- Jensen, K.K.; Orum, H.; Nielsen, P.E.; Nordén, B. Kinetics for hybridization of peptide nucleic acids (PNA) with DNA and RNA studied with the BIAcore technique. Biochemistry 1997, 36, 5072–5077. [Google Scholar] [CrossRef] [PubMed]
- Demidov, V.V.; Potaman, V.N.; Frank-Kamenetskii, M.D.; Egholm, M.; Buchard, O.; Sönnichsen, S.H.; Nielsen, P.E. Stability of peptide nucleic acids in human serum and cellular extracts. Biochem. Pharmacol. 1994, 48, 1310–1313. [Google Scholar] [CrossRef]
- Robaczewska, M.; Narayan, R.; Seigneres, B.; Schorr, O.; Thermet, A.; Podhajska, A.J.; Trepo, C.; Zoulim, F.; Nielsen, P.E.; Cova, L. Sequence-specific inhibition of duck hepatitis B virus reverse transcription by peptide nucleic acids (PNA). J. Hepatol. 2005, 42, 180–187. [Google Scholar] [CrossRef] [PubMed]
- Ndeboko, B.; Lemamy, G.J.; Nielsen, P.E.; Cova, L. Therapeutic Potential of Cell Penetrating Peptides (CPPs) and Cationic Polymers for Chronic Hepatitis B. Int. J. Mol. Sci. 2015, 16, 28230–28241. [Google Scholar] [CrossRef] [PubMed]
- Ndeboko, B.; Ramamurthy, N.; Lemamy, G.J.; Jamard, C.; Nielsen, P.E.; Cova, L. Role of Cell-Penetrating Peptides in Intracellular Delivery of Peptide Nucleic Acids Targeting Hepadnaviral Replication. Mol. Ther. Nucleic Acids 2017, 9, 162–169. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.H.; Chen, C.P.; Chan, M.H.; Chang, M.; Hou, Y.W.; Chen, H.H.; Hsu, H.R.; Liu, K.; Lee, H.J. Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells. Biochem. Biophys. Res. Commun. 2006, 346, 758–767. [Google Scholar] [CrossRef] [PubMed]
- Nakamura, Y.; Kogure, K.; Futaki, S.; Harashima, H. Octaarginine-modified multifunctional envelope-type nano device for siRNA. J. Control. Release 2007, 119, 360–367. [Google Scholar] [CrossRef] [PubMed]
- Khalil, I.A.; Kogure, K.; Futaki, S.; Harashima, H. Octaarginine-modified liposomes: Enhanced cellular uptake and controlled intracellular trafficking. Int. J. Pharm. 2008, 354, 39–48. [Google Scholar] [CrossRef] [PubMed]
- Gemignani, F.; Kang, S.H.; Maier, M.A.; Manoharan, M.; Persmark, M.; Bortner, D.; Kole, R. Systemically delivered antisense oligomers upregulate gene expression in mouse tissues. Nat. Biotechnol. 2002, 20, 1228–1233. [Google Scholar]
- Abes, S.; Williams, D.; Prevot, P.; Thierry, A.; Gait, M.J.; Lebleu, B. Endosome trapping limits the efficiency of splicing correction by PNA-oligolysine conjugates. J. Control. Release 2006, 110, 595–604. [Google Scholar] [CrossRef] [PubMed]
- Zoulim, F.; Saade, F.; Buronfosse, T.; Abdul, F.; Cova, L. Animal models for the study of infection. In Hepatitis B Virus; Locarnini, S., Lai, C.L., Eds.; International Medical Press: London, UK, 2008; Volume I, pp. 6.1–6.20. [Google Scholar]
- Rollier, C.; Sunyach, C.; Barraud, L.; Madani, N.; Jamard, C.; Trepo, C.; Cova, L. Protective and therapeutic effect of DNA-based immunization against hepadnavirus large envelope protein. Gastroenterology 1999, 116, 658–665. [Google Scholar] [CrossRef]
- Robaczewska, M.; Narayan, R.; Seigneres, B.; Schorr, O.; Thermet, A.; Podhajska, A.J.; Trepo, C.; Zoulim, F.; Nielsen, P.E.; Cova, L. Inhibition of hepadnaviral replication by polyethylenimine-based intravenous delivery of antisense phosphodiester oligodeoxynucleotides to the liver. Gene Ther. 2001, 8, 874–881. [Google Scholar] [CrossRef] [PubMed]
- Borel, C.; Schorr, O.; Durand, I.; Zoulim, F.; Kay, A.; Trepo, C.; Hantz, O. Initial amplification of duck hepatitis B virus covalently closed circular DNA after in vitro infection of embryonic duck hepatocytes is increased by cell cycle progression. Hepatology 2001, 34, 168–179. [Google Scholar] [CrossRef] [PubMed]
- Seignères, B.; Martin, P.; Werle, B.; Schorr, O.; Jamard, C.; Rimsky, L.; Trépo, C.; Zoulim, F. Effects of pyrimidine and purine analog combinations in the duck hepatitis B virus infection model. Antimicrob. Agents Chemother. 2003, 47, 1842–1852. [Google Scholar] [CrossRef] [PubMed]
- Cova, L.; Zoulim, F. Duck hepatitis B virus model in the study of hepatitis B virus. Methods Mol. Med. 2004, 96, 261–268. [Google Scholar] [PubMed]
- Quinet, J.; Jamard, C.; Burtin, M.; Lemasson, M.; Guerret, S.; Sureau, C.; Vaillant, A.; Cova, L. Nucleic acid polymer REP 2139 and nucleos(T)ide analogues act synergistically against chronic hepadnaviral infection in vivo in Pekin ducks. Hepatology 2018, 67, 2127–2140. [Google Scholar] [CrossRef] [PubMed]
- Abdul, F.; Ndeboko, B.; Buronfosse, T.; Zoulim, F.; Kann, M.; Nielsen, P.E.; Cova, L. Potent inhibition of late stages of hepadnavirus replication by a modified cell penetrating peptide. PLoS ONE 2012, 7, e48721. [Google Scholar] [CrossRef] [PubMed]
- Sebbage, V. Cell-penetrating peptides and their therapeutic applications. Biosci. Horiz. 2009, 2, 64–72. [Google Scholar] [CrossRef]
- Xun, Y.; Pan, Q.; Tang, Z.; Chen, X.; Yu, Y.; Xi, M.; Zang, G. Intracellular-delivery of a single-chain antibody against hepatitis B core protein via cell-penetrating peptide inhibits hepatitis B virus replication in vitro. Int. J. Mol. Med. 2013, 31, 369–376. [Google Scholar] [CrossRef] [PubMed]
- Holm, T.; Johansson, H.; Lundberg, P.; Pooga, M.; Lindgren, M.; Langel, U. Studying the uptake of cell-penetrating peptides. Nat. Protoc. 2006, 1, 1001–1005. [Google Scholar] [CrossRef] [PubMed]
- Mae, M.; Langel, U. Cell-penetrating peptides as vectors for peptide, protein and oligonucleotide delivery. Curr. Opin. Pharmacol. 2006, 6, 509–514. [Google Scholar] [CrossRef] [PubMed]
- Bendifallah, N.; Rasmussen, F.W.; Zachar, V.; Ebbesen, P.; Nielsen, P.E.; Koppelhus, U. Evaluation of cell-penetrating peptides (CPPs) as vehicles for intracellular delivery of antisense peptide nucleic acid (PNA). Bioconjugate Chem. 2006, 17, 750–758. [Google Scholar] [CrossRef] [PubMed]
- Ruczynski, J.; Wierzbicki, P.M.; Kogut-Wierzbicka, M.; Mucha, P.; Siedlecka-Kroplewska, K.; Rekowski, P. Cell-penetrating peptides as a promising tool for delivery of various molecules into the cells. Folia Histochem. Cytobiol. 2014, 52, 257–269. [Google Scholar] [CrossRef] [PubMed]
- Green, M.; Loewenstein, P.M. Autonomous functional domains of chemically synthesized human immunodeficiency virus TAT trans-activator protein. Cell 1988, 55, 1179–1188. [Google Scholar] [CrossRef]
- Frankel, A.D.; Pabo, C.O. Cellular uptake of the TAT protein from human immunodeficiency virus. Cell 1988, 55, 1189–1193. [Google Scholar] [CrossRef]
- Song, J.; Zhang, Y.; Zhang, W.; Chen, J.; Yang, X.; Ma, P.; Zhang, B.; Liu, B.; Ni, J.; Wang, R. Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin. Peptides 2015, 63, 143–149. [Google Scholar] [CrossRef] [PubMed]
- Kumar, M.; Tegge, W.; Wangoo, N.; Jain, R.; Sharma, R.K. Insights into cell penetrating peptide conjugated gold nanoparticles for internalization into bacterial cells. Biophys. Chem. 2018, 237, 38–46. [Google Scholar] [CrossRef] [PubMed]
- Elliott, G.; O’Hare, P. Intercellular trafficking and protein delivery by a herpesvirus structural protein. Cell 1997, 88, 223–233. [Google Scholar] [CrossRef]
- Joliot, A.; Pernelle, C.; Deagostini-Bazin, H.; Prochiantz, A. Antennapedia homeobox peptide regulates neural morphogenesis. Proc. Natl. Acad. Sci. USA 1991, 88, 1864–1868. [Google Scholar] [CrossRef] [PubMed]
- Derossi, D.; Joliot, A.H.; Chassaing, G.; Prochiantz, A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem. 1994, 269, 10444–10450. [Google Scholar] [PubMed]
- Montrose, K.; Yang, Y.; Krissansen, G.W. X-pep, a novel cell-penetrating peptide motif derived from the hepatitis B virus. Biochem. Biophys. Res. Commun. 2014, 453, 64–68. [Google Scholar] [CrossRef] [PubMed]
- Schwarze, S.R.; Ho, A.; Vocero-Akbani, A.; Dowdy, S.F. In vivo protein transduction: Delivery of a biologically active protein into the mouse. Science 1999, 285, 1569–1572. [Google Scholar] [CrossRef] [PubMed]
- Zorko, M.; Langel, U. Cell-penetrating peptides: Mechanism and kinetics of cargo delivery. Adv. Drug Deliv. Rev. 2005, 57, 529–545. [Google Scholar] [CrossRef] [PubMed]
- Brown, K.L.; Hancock, R.E. Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol. 2006, 18, 24–30. [Google Scholar] [CrossRef] [PubMed]
- Jensen, H.L. Herpes simplex virus type 1 morphogenesis and virus-cell interactions: Significance of cytoskeleton and methodological aspects. APMIS Suppl. 2006, 114, 7–55. [Google Scholar] [CrossRef] [PubMed]
- Lizzi, A.R.; Carnicelli, V.; Clarkson, M.M.; Di Giulio, A.; Oratore, A. Lactoferrin derived peptides: Mechanisms of action and their perspectives as antimicrobial and antitumoral agents. Mini Rev. Med. Chem. 2009, 9, 687–695. [Google Scholar] [CrossRef] [PubMed]
- Egal, M.; Conrad, M.; MacDonald, D.L.; Maloy, W.L.; Motley, M.; Genco, C.A. Antiviral effects of synthetic membrane-active peptides on herpes simplex virus, type 1. Int. J. Antimicrob. Agents 1999, 13, 57–60. [Google Scholar] [CrossRef]
- Albiol Matanic, V.C.; Castilla, V. Antiviral activity of antimicrobial cationic peptides against Junin virus and herpes simplex virus. Int. J. Antimicrob. Agents 2004, 23, 382–389. [Google Scholar] [CrossRef] [PubMed]
- Roisin, A.; Robin, J.P.; Dereuddre-Bosquet, N.; Vitte, A.L.; Dormont, D.; Clayette, P.; Jalinot, P. Inhibition of HIV-1 replication by cell-penetrating peptides binding Rev. J. Biol. Chem. 2004, 279, 9208–9214. [Google Scholar] [CrossRef] [PubMed]
- Hancock, R.E.; Diamond, G. The role of cationic antimicrobial peptides in innate host defences. Trends Microbiol. 2000, 8, 402–410. [Google Scholar] [CrossRef]
- Li, Y.; Li, Y.; Wang, X.; Lee, R.J.; Teng, L. Fatty acid modified octa-arginine for delivery of siRNA. Int. J. Pharm. 2015, 495, 527–535. [Google Scholar] [CrossRef] [PubMed]
- Bruss, V. Envelopment of the hepatitis B virus nucleocapsid. Virus Res. 2004, 106, 199–209. [Google Scholar] [CrossRef] [PubMed]
- Lambert, C.; Döring, T.; Prange, R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and γ2-adaptin. J. Virol. 2007, 81, 9050–9060. [Google Scholar] [CrossRef] [PubMed]
- Pan, X.B.; Wei, L.; Han, J.C.; Ma, H.; Deng, K.; Cong, X. Artificial recombinant cell-penetrating peptides interfere with envelopment of hepatitis B virus nucleocapsid and viral production. Antivir. Res. 2011, 89, 109–114. [Google Scholar] [CrossRef] [PubMed]
- Mhamdi, M.; Funk, A.; Hohenberg, H.; Will, H.; Sirma, H. Assembly and budding of a hepatitis B virus is mediated by a novel type of intracellular vesicles. Hepatology 2007, 46, 95–106. [Google Scholar] [CrossRef] [PubMed]
- Köck, J.; Rösler, C.; Zhang, J.J.; Blum, H.E.; Nassal, M.; Thoma, C. Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner. PLoS Pathog. 2010, 6, e1001082. [Google Scholar] [CrossRef] [PubMed]
- Wang, G.H.; Seeger, C. Novel mechanism for reverse transcription in hepatitis B viruses. J. Virol. 1993, 67, 6507–6512. [Google Scholar] [PubMed]
- Nassal, M.; Junker-Niepmann, M.; Schaller, H. Translational inactivation of RNA function: Discrimination against a subset of genomic transcripts during HBV nucleocapsid assembly. Cell 1990, 63, 1357–1363. [Google Scholar] [CrossRef]
- Chu, X.; Wu, B.; Fan, H.; Hou, J.; Hao, J.; Hu, J.; Wang, B.; Liu, G.; Li, C.; Meng, S. PTD-fused p53 as a potential antiviral agent directly suppresses HBV transcription and expression. Antivir. Res. 2016, 127, 41–49. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Liu, H.; Tang, Z.; Yu, Y.; Zang, G. The modification of Tapasin enhances cytotoxic T lymphocyte activity of intracellularly delivered CTL epitopes via cytoplasmic transduction peptide. Acta Biochim. Biophys. Sin. 2013, 45, 203–212. [Google Scholar] [CrossRef] [PubMed]
- Morell, A.G.; Irvine, R.A.; Sternlieb, I.; Scheinberg, I.H.; Ashwell, G. Physical and chemical studies on ceruloplasmin. V. Metabolic studies on sialic acid-free ceruloplasmin in vivo. J. Biol. Chem. 1968, 243, 155–159. [Google Scholar] [PubMed]
- Faivre, V.; Fessi, H. Thérapie génique et vecteurs non-viraux: Ière partie—Des systèmes multiples. Lyon Pharm. 2000, 51, 1–13. [Google Scholar]
- Obara, K.; Ishihara, T.; Akaike, T.; Maruyama, A. Protein/oligonucleotide conjugates as a cell specific PNA carrier. Nucleic Acids Res. 2001, 1, 217–218. [Google Scholar] [CrossRef]
- Monsigny, M.; Rondanino, C.; Duverger, E.; Fajac, I.; Roche, A.C. Glyco-dependent nuclear import of glycoproteins, glycoplexes and glycosylated plasmids. Biochim. Biophys. Acta 2004, 1673, 94–103. [Google Scholar] [CrossRef] [PubMed]
- Ishihara, T.; Kano, A.; Obara, K.; Saito, M.; Chen, X.; Park, T.G.; Akaike, T.; Maruyama, A. Nuclear localization and antisense effect of PNA internalized by ASGP-R-mediated endocytosis with protein/DNA conjugates. J. Control. Release 2011, 155, 34–39. [Google Scholar] [CrossRef] [PubMed]
- Gripon, P.; Rumin, S.; Urban, S.; Le Seyec, J.; Glaise, D.; Cannie, I.; Guyomard, C.; Lucas, J.; Trepo, C.; Guguen-Guillouzo, C. Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. USA 2002, 99, 15655–15660. [Google Scholar] [CrossRef] [PubMed]
- Hantz, O.; Parent, R.; Durantel, D.; Gripon, P.; Guguen-Guillouzo, C.; Zoulim, F. Persistence of the hepatitis B virus covalently closed circular DNA in HepaRG human hepatocyte-like cells. J. Gen. Virol. 2009, 90 Pt 1, 127–135. [Google Scholar] [CrossRef] [PubMed]
- Ali, S.A.; Teow, S.Y.; Omar, T.C.; Khoo, A.S.; Choon, T.S.; Yusoff, N.M. A Cell Internalizing Antibody Targeting Capsid Protein (p24) Inhibits the Replication of HIV-1 in T Cells Lines and PBMCs: A Proof of Concept Study. PLoS ONE 2016, 11, e0145986. [Google Scholar] [CrossRef] [PubMed]
- Keogan, S.; Passic, S.; Krebs, F.C. Infection by CXCR4-Tropic Human Immunodeficiency Virus Type 1 Is Inhibited by the Cationic Cell-Penetrating Peptide Derived from HIV-1 Tat. Int. J. Pept. 2012, 349427. [Google Scholar] [CrossRef] [PubMed]
- Bivalkar-Mehla, S.; Mehla, R.; Chauhan, A. Chimeric peptide-mediated siRNA transduction to inhibit HIV-1 infection. J. Drug Target. 2017, 25, 307–319. [Google Scholar] [CrossRef] [PubMed]
- Yoo, J.S.; Kim, C.M.; Kim, J.H.; Kim, J.Y.; Oh, J.W. Inhibition of Japanese encephalitis virus replication by peptide nucleic acids targeting cis-acting elements on the plus- and minus-strands of viral RNA. Antivir. Res. 2009, 82, 122–133. [Google Scholar] [CrossRef] [PubMed]
- Mino, T.; Mori, T.; Aoyama, Y.; Sera, T. Development of protein-based antiviral drugs for human papillomaviruses. Nucleic Acids Symp. Ser. 2007, 51, 427–428. [Google Scholar] [CrossRef] [PubMed]
- Mino, T.; Mori, T.; Aoyama, Y.; Sera, T. Cell-permeable artificial zinc-finger proteins as potent antiviral drugs for human papillomaviruses. Arch. Virol. 2008, 153, 1291–1298. [Google Scholar] [CrossRef] [PubMed]
CPPs | Cell or Animal Models | Target | % D’inhibition | Toxicity |
---|---|---|---|---|
(DArg)8 | PDHs | DHBV | 44–60% (2 μM) | [10,23] |
Pekin ducklings | DHBV | 42% (1 μg/g/bw/day) | – [10] | |
Decanoyl(DArg)8 | PDHs | DHBV | 86–90% (2 μM) | – [23] |
LMH-D2 | DHBV | 88–90% (2 μM) | – [23] | |
HepG2.2.15 | HBV | 50% (4 μM) | – [23] | |
(DArg)8-PNA | PDHs | DHBV Epsilon (ε) | 47–59% (2 μM) | – [10] |
Pekin ducklings | DHBV Epsilon (ε) | 49–59% (1 μg/g/bw/day) | – [10] |
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Ndeboko, B.; Hantz, O.; Lemamy, G.J.; Cova, L. Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway. Biomolecules 2018, 8, 55. https://doi.org/10.3390/biom8030055
Ndeboko B, Hantz O, Lemamy GJ, Cova L. Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway. Biomolecules. 2018; 8(3):55. https://doi.org/10.3390/biom8030055
Chicago/Turabian StyleNdeboko, Bénédicte, Olivier Hantz, Guy Joseph Lemamy, and Lucyna Cova. 2018. "Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway" Biomolecules 8, no. 3: 55. https://doi.org/10.3390/biom8030055
APA StyleNdeboko, B., Hantz, O., Lemamy, G. J., & Cova, L. (2018). Developments in Cell-Penetrating Peptides as Antiviral Agents and as Vehicles for Delivery of Peptide Nucleic Acid Targeting Hepadnaviral Replication Pathway. Biomolecules, 8(3), 55. https://doi.org/10.3390/biom8030055