Skip to main content

Advertisement

SpringerLink
Log in

siRNA intervention inhibiting viral replication and delivery strategies for treating herpes simplex viral infection

  • Commentary
  • Published:
VirusDisease Aims and scope Submit manuscript

Abstract

The effective treatment of herpes simplex virus (HSV) infections generally involves the use of antiviral nucleoside drugs, but with increasing reports of antiviral resistance, the use of these drugs is challenged. Hence, a need arises to explore alternate treatment options. In this review we have discussed various targets that have been explored to control the HSV replication using siRNA therapeutics. We have also discussed the advantages of targeting a less explored UL10 gene to develop an alternate therapeutic intervention. Gene silencing can induce an inhibitory activity to virus spread and infection. The capacity and suitability of UL10 gene as siRNA induced silencing target in eliciting the desired antiviral effect in patients is identified and particularly discussed. The major challenge associated with the siRNA therapeutics is their delivery. The various viable delivery options, that are being explored in the recent times is summarized and different delivery pathways and strategies are reviewed as a part of the study.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Blondeau C, Pelchen-Matthews A, Mlcochova P, Marsh M, Milne R, Towers G. Tetherin restricts herpes simplex virus 1 and Is antagonized by glycoprotein M. J Virol. 2013;87(24):13124–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Chouljenko D, Kim I, Chouljenko V, Subramanian R, Walker J, Kousoulas K. Functional hierarchy of herpes simplex virus 1 viral glycoproteins in cytoplasmic virion envelopment and egress. J Virol. 2012;86(8):4262–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Crump CM, Bruun B, Bell S, Pomeranz LE, Minson T, Browne HM. Alpha herpesvirus glycoprotein M causes the relocalization of plasma membrane proteins. J Gen Virol. 2004;85:3517–27.

    Article  CAS  PubMed  Google Scholar 

  4. da Silva A, Lopes JF, Paula VS. RNA interference inhibits herpes simplex virus type 1 isolated from saliva samples and mucocutaneous lesions. Braz J Infect Dis. 2014;18(4):441–4.

    Article  PubMed  Google Scholar 

  5. da Silva A, Raposo JV, Pereira TC, Pinto MA, de Paula VS. Effects of RNA interference therapy against herpes simplex virus type 1 encephalitis. Antivir Ther. 2016;20(3):225–35.

    Article  Google Scholar 

  6. 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.

    Article  PubMed  Google Scholar 

  7. El Kasmi I, Lippé R. Herpes simplex virus 1 gN partners with gM To modulate the viral fusion machinery. J Virol. 2015;89(4):2313–23.

    Article  CAS  PubMed  Google Scholar 

  8. Gavrilov K, Saltzman W. Therapeutic siRNA: principles, challenges, and strategies. Yale J Biol Med. 2012;85:187–200.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Gilleron J, Paramasivam P, Zeigerer A, Querbes W, Marsico G, Andree C, Seifert S, Amaya P, Stöter M, Koteliansky V, Waldmann H, Fitzgerald K, Kalaidzidis Y, Akinc A, Maier M, Manoharan M, Bickle M, Zerial M. Identification of siRNA delivery enhancers by a chemical library screen. Nucleic Acids Res. 2015;43(16):7984–8001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hochberg CH, Schneider JA, Dandona R, Lakshmi V, Kumar GA, Sudha T, Akbar M, Ahmed GMM, Ramgopal SP, Armbruster B, Alary M, Dandona L. Population and dyadic-based seroincidence of herpes simplex virus-2 and syphilis in southern India. Sex Transm Infect. 2015;91(5):375–82.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jiang Y, Huo S, Hardie J, Liang X, Rotello V. Progress and perspective of inorganic nanoparticle-based siRNA delivery systems. Expert Opin Drug Deliv. 2016;13(4):547–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Jin F, Li S, Zheng K, Zhuo C, Ma K, Chen M, Wang Q, Zhang P, Fan J, Ren Z, Wang Y. Silencing herpes simplex virus type 1 capsid protein encoding genes by siRNA: a promising antiviral therapeutic approach. PLOS ONE. 2014;9(5):96623.

    Article  CAS  Google Scholar 

  13. Kim I, Chouljenko V, Walker J, Kousoulas K. Herpes simplex virus 1 glycoprotein M and the membrane-associated protein UL11 are required for virus-induced cell fusion and efficient virus entry. J Virol. 2013;87(14):8029–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kodama Y, Shiokawa Y, Nakamura T, Kurosaki T, Aki K, Nakagawa H, Muro T, Kitahara T, Higuchi N, Sasaki H. Novel siRNA delivery system using a ternary polymer complex with strong silencing effect and no cytotoxicity. Biol Pharm Bull. 2014;37(8):1274–81.

    Article  CAS  PubMed  Google Scholar 

  15. Kozielski K, Tzeng S, Green J. Bioengineered nanoparticles for siRNA delivery. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnol. 2013;5(5):449–68.

    CAS  Google Scholar 

  16. Lau S, Crump C. HSV-1 gM and the gK/pUL20 complex are important for the localization of gD and gH/L to viral assembly sites. Viruses. 2015;7(3):915–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Leege T, Fuchs W, Granzow H, Kopp M, Klupp B, Mettenleiter T. Effects of simultaneous deletion of pUL11 and glycoprotein M on virion maturation of herpes simplex virus type 1. J Virol. 2008;83(2):896–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. MacLean C, Robertson L, Jamieson F. Characterization of the UL10 gene product of herpes simplex virus type 1 and investigation of its role in vivo. J Gen Virol. 1993;74(6):975–83.

    Article  CAS  PubMed  Google Scholar 

  19. Paavilainen H, Lehtinen J, Romanovskaya A, Nygårdas M, Bamford DH, Poranen MM, Hukkanen V. Inhibition of clinical pathogenic herpes simplex virus 1 strains with enzymatically created siRNA pools. J Med Virol. 2016;88(12):2196–205.

    Article  CAS  PubMed  Google Scholar 

  20. Paavilainen H, Lehtinen J, Romanovskaya A, Nygårdas M, Bamford DH, Poranen MM, Hukkanen V. Topical treatment of herpes simplex virus infection with enzymatically created siRNA swarm. Antivir Ther. 2017;22(7):631–7.

    Article  CAS  PubMed  Google Scholar 

  21. Patwardhan V, Bhalla P. Role of type-specific herpes simplex virus-1 and 2 serology as a diagnostic modality in patients with clinically suspected genital herpes: a comparative study in Indian population from a tertiary care hospital. Indian J Pathol Microbiol. 2016;59(3):318–21.

    Article  PubMed  Google Scholar 

  22. Ren Y, Bell S, Zenner H, Lau S, Crump C. Glycoprotein M is important for the efficient incorporation of glycoprotein H–L into herpes simplex virus type 1 particles. J Gen Virol. 2011;93(2):319–29.

    Article  CAS  PubMed  Google Scholar 

  23. Salzano G, Costa D, Torchilin V. siRNA delivery by stimuli-sensitive nanocarriers. Curr Pharm Des. 2015;21(31):4566–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Saran N, Bupesh G, Magesh S, Vennila S, Anandharaj B, Anupama CP, Kaveri K, Gunasekaran P. Epidemiological studies and molecular characterization of herpes simplex virus among Urban population in Chennai, Tamilnadu. Epidemiol: Open Access. 2015;5(02):187.

    Google Scholar 

  25. Sarett S, Nelson C, Duvall C. Technologies for controlled, local delivery of siRNA. J Control Release. 2015;218:94–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shim M, Kwon Y. Efficient and targeted delivery of siRNA in vivo. FEBS J. 2010;277(23):4814–27.

    Article  CAS  PubMed  Google Scholar 

  27. Song B, Liu X, Wang Q, Zhang R, Yang T, Han Z, Xu Y. Adenovirus-mediated shRNA interference against HSV-1 replication in vitro. J Neurovirol. 2016;22(6):799–807.

    Article  CAS  PubMed  Google Scholar 

  28. Striebinger H, Funk C, Raschbichler V, Bailer S. Subcellular trafficking and functional relationship of the HSV-1 glycoproteins N and M. Viruses. 2016;8(3):83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tatiparti K, Sau S, Kashaw S, Iyer A. siRNA delivery strategies: a comprehensive review of recent developments. Nanomaterials. 2017;7(4):77.

    Article  CAS  PubMed Central  Google Scholar 

  30. Wang J, Lu Z, Wientjes M, Au J. Delivery of siRNA therapeutics: barriers and carriers. AAPS J. 2010;12(4):492–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang Z, Fan P, Zhao Y, Zhang S, Lu J, Xie W, Jiang Y, Lei F, Xu N. NEAT1 modulates herpes simplex virus-1 replication by regulating viral gene transcription. Cell Mol Life Sci. 2017;74(6):1117–31.

    Article  CAS  PubMed  Google Scholar 

  32. Whitley R, Kimberlin D, Roizman B. Herpes simplex viruses. Clin Infect Dis. 1998;26(3):541–53.

    Article  CAS  Google Scholar 

  33. Wu Y, Navarro F, Lal A, Basar E, Pandey RK, Manoharan M, Feng Y, Lee SJ, Lieberman J, Palliser D. Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene. Cell Host Microbe. 2009;5:84–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xu C, Wang J. Delivery systems for siRNA drug development in cancer therapy. Asian J Pharm Sci. 2015;10(1):1–12.

    Article  Google Scholar 

  35. Zhang Y, Lai W, Li H, Li G. Inhibition of herpes simplex virus type 1 by small interfering RNA. Clin Exp Dermatol. 2008;33(1):56–61.

    CAS  PubMed  Google Scholar 

  36. Zhang J, Nagel C, Sodeik B, Lippe R. Early, active, and specific localization of herpes simplex virus type 1 gM to nuclear membranes. J Virol. 2009;83(24):12984–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India

    Vyshnavi Manda, Venkata Rao Josyula & Raghu Chandrashekar Hariharapura

  2. Manipal McGill Centre for Infectious Diseases, Prasanna School of Public Health, Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, 576104, India

    Raghu Chandrashekar Hariharapura

Authors
  1. Vyshnavi Manda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Venkata Rao Josyula
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raghu Chandrashekar Hariharapura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raghu Chandrashekar Hariharapura.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Manda, V., Josyula, V. & Hariharapura, R. siRNA intervention inhibiting viral replication and delivery strategies for treating herpes simplex viral infection. VirusDis. 30, 180–185 (2019). https://doi.org/10.1007/s13337-018-00508-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13337-018-00508-z

Keywords

Search

Navigation