Investigating the Safety and Efficacy of the Synthetic Drug Herbix on Immune Responses Involved in the Treatment of a Mouse Model of Herpes Simplex Virus
Abstract
Herpes simplex virus-1 (HSV-1) infections can cause significant harm to individuals, including blindness, congenital defects, genital herpes, and even cancer, with no definitive cure .so, finding new treatment strategies is crucial.
In this study, 25 male BALB/c mice were used to conduct a mouse model of herpes by subcutaneously injecting an HSV-1 suspension (100 µL of 1× PFU/mL). The mice were divided into 5 groups with groups 1 to 3 designated as intervention groups, and groups 4 and 5 serving as positive and negative control groups, respectively. After 2 days of virus inoculation, the mice were treated with different concentrations of Herbix (100, 200, and 300 mg/mL) via subcutaneous injection. Mice Blood samples (0.5 to 1 mL) were taken from the mice before and after the experiments, and after three-week follow-up period, the mice were sacrificed and the spleens were removed for lymphocyte analysis.
we found that administration of Herbix at a dose of 300 mg/mL showed the greatest efficacy, characterized by a delay in skin lesion formation, an increment in survival rate and lymphocyte proliferation, upregulation of the gene expression of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α), and an increase in the polarization of cytotoxic and helper T lymphocytes compared to the control group.
These results suggest that Herbix at a dose of 300 mg/mL is effective in treating murine herpes and stimulating immune responses, making it a potential candidate for further investigation as an antiherpetic drug.
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16. Oberman F, Panet A. Inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells. J Gen Virol. 1988;69(6):1167-77.
17. Bouley DM, Kanangat S, Rouse BT. The role of the innate immune system in the reconstituted SCID mouse model of herpetic stromal keratitis. Clin Immunol immunopathol. 1996;80(1):23-30.
18. Paladino P, Mossman KL. Mechanisms employed by herpes simplex virus 1 to inhibit the interferon response. J Interferon Cytokine Res. 2009;29(9):599-608.
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20. Horiuchi Y. Th1 regulatory events by infectious pathogens, herpes zoster and herpes simplex viruses: prospects for therapeutic options for atopic eczema. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2022;39(4):662-7.
21. Billiau A, Heremans H, Vermeire K, Matthys P. Immunomodulatory Properties of Interferon‐γ: An Update a. Ann N Y Acad Sci. 1998;856(1):22-32.
22. Boeren M, Meysman P, Laukens K, Ponsaerts P, Ogunjimi B, Delputte P. T cell immunity in HSV-1-and VZV-infected neural ganglia. Trends Microbiol. 2023;31(1):51-61.
23. Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature. 2009;462(7272):510-3.
24. O’Neil TR, Hu K, Truong NR, Arshad S, Shacklett BL, Cunningham AL, et al. The role of tissue resident memory CD4 T cells in herpes simplex viral and HIV infection. Viruses. 2021;13(3):359.
25. Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A. CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proc Natl Acad Sci U S A. 2011;108(21):8749-54.
26. Rajasagi NK, Kassim SH, Kollias CM, Zhao X, Chervenak R, Jennings SR. CD4+ T cells are required for the priming of CD8+ T cells following infection with herpes simplex virus type 1. J Virol. 2009;83(10):5256-68.
27. Gmyrek GB, Predki P, Gershburg E, Carr DJ. Noncognate Signals Drive Enhanced Effector CD8+ T Cell Responses through an IFNAR1-Dependent Pathway after Infection with the Prototypic Vaccine, 0ΔNLS, against Herpes Simplex Virus 1. J Virol. 2022;96(6):e01724-21.
28. Larsen H, Russell R, Rouse B. Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes. Infect Immun. 1983;41(1):197-204.
29. Wang Y-S, Liu D, Wang X, Luo Q-L, Ding L, Fan D-Y, et al. Rasmussen’s encephalitis is characterized by relatively lower production of IFN-β and activated cytotoxic T cell upon herpes viruses infection. J Neuroinflammation. 2022;19(1):1-15.
2. Zhu S, Viejo-Borbolla A. Pathogenesis and virulence of herpes simplex virus. Virulence. 2021;12(1):2670-2702.
3. Koujah L, Suryawanshi RK, Shukla D. Pathological processes activated by herpes simplex virus-1 (HSV-1) infection in the cornea. Cell Mol Life Sci. 2019;76(3):405-419.
4. Whitford AL, Cliffe AR. Key questions on the epigenetics of herpes simplex virus latency. Plos Pathogens. 2022;18(6):1010587.
5. St. Leger AJ, Koelle DM, Kinchington PR, Verjans GMG. Local immune control of latent herpes simplex virus type 1 in ganglia of mice and man. Front Immunol. 2021;12:723809.
6. Artusi S, Ruggiero E, Nadai M, Tosoni B, Perrone R, Ferino A, et al. Antiviral activity of the G-quadruplex ligand TMPyP4 against Herpes Simplex Virus-1. Viruses. 2021;13(2):196.
7. Pisitpayat P, Jongkhajornpong P, Lekhanont K, Nonpassopon M. Role of Intravenous Acyclovir in Treatment of Herpes Simplex Virus Stromal Keratitis with Ulceration: A Review of 2 Cases. Am J Case Rep 2021;22:930467-1.
8. Markert JM, Gillespie GY, Weichselbaum RR, Roizman B, Whitley RJ. Genetically engineered HSV in the treatment of glioma: a review. Rev Med virol. 2000;10(1):17-30.
9. Stanberry LR. Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines. Herpes. 2004;11:161A-9
10. Bag P, Chattopadhyay D, Mukherjee H, Ojha D, Mandal N, Sarkar MC, et al. Anti-herpes virus activities of bioactive fraction and isolated pure constituent of Mallotus peltatus: an ethnomedicine from Andaman Islands. Virol J. 2012;9(1):1-12.
11. Lipipun V, Kurokawa M, Suttisri R, Taweechotipatr P, Pramyothin P, Hattori M, et al. Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res. 2003;60(3):175-80.
12. Malik F, Singh J, Khajuria A, Suri KA, Satti NK, Singh S, et al. A standardized root extract of Withania somnifera and its major constituent withanolide-A elicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB/c mice. Life Sci. 2007;80(16):1525-38.
13. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
14. Kurokawa M, Ochiai H, Nagasaka K, Neki M, Xu H, Kadota S, et al. Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice. Antiviral Res. 1993;22(2-3):175-88.
15. Owlia P, Saderi H, Aghaee H, Zayeri F. The effect of Myrtus communis L. essential oil on treatment of Herpes simplex infection in animal model. Iran J Med Aromatic Plants Res. 2007;23(2):157-65.
16. Oberman F, Panet A. Inhibition of transcription of herpes simplex virus immediate early genes in interferon-treated human cells. J Gen Virol. 1988;69(6):1167-77.
17. Bouley DM, Kanangat S, Rouse BT. The role of the innate immune system in the reconstituted SCID mouse model of herpetic stromal keratitis. Clin Immunol immunopathol. 1996;80(1):23-30.
18. Paladino P, Mossman KL. Mechanisms employed by herpes simplex virus 1 to inhibit the interferon response. J Interferon Cytokine Res. 2009;29(9):599-608.
19. Kidd P. Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev. 2003;8(3):223-46.
20. Horiuchi Y. Th1 regulatory events by infectious pathogens, herpes zoster and herpes simplex viruses: prospects for therapeutic options for atopic eczema. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2022;39(4):662-7.
21. Billiau A, Heremans H, Vermeire K, Matthys P. Immunomodulatory Properties of Interferon‐γ: An Update a. Ann N Y Acad Sci. 1998;856(1):22-32.
22. Boeren M, Meysman P, Laukens K, Ponsaerts P, Ogunjimi B, Delputte P. T cell immunity in HSV-1-and VZV-infected neural ganglia. Trends Microbiol. 2023;31(1):51-61.
23. Nakanishi Y, Lu B, Gerard C, Iwasaki A. CD8+ T lymphocyte mobilization to virus-infected tissue requires CD4+ T-cell help. Nature. 2009;462(7272):510-3.
24. O’Neil TR, Hu K, Truong NR, Arshad S, Shacklett BL, Cunningham AL, et al. The role of tissue resident memory CD4 T cells in herpes simplex viral and HIV infection. Viruses. 2021;13(3):359.
25. Kumamoto Y, Mattei LM, Sellers S, Payne GW, Iwasaki A. CD4+ T cells support cytotoxic T lymphocyte priming by controlling lymph node input. Proc Natl Acad Sci U S A. 2011;108(21):8749-54.
26. Rajasagi NK, Kassim SH, Kollias CM, Zhao X, Chervenak R, Jennings SR. CD4+ T cells are required for the priming of CD8+ T cells following infection with herpes simplex virus type 1. J Virol. 2009;83(10):5256-68.
27. Gmyrek GB, Predki P, Gershburg E, Carr DJ. Noncognate Signals Drive Enhanced Effector CD8+ T Cell Responses through an IFNAR1-Dependent Pathway after Infection with the Prototypic Vaccine, 0ΔNLS, against Herpes Simplex Virus 1. J Virol. 2022;96(6):e01724-21.
28. Larsen H, Russell R, Rouse B. Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes. Infect Immun. 1983;41(1):197-204.
29. Wang Y-S, Liu D, Wang X, Luo Q-L, Ding L, Fan D-Y, et al. Rasmussen’s encephalitis is characterized by relatively lower production of IFN-β and activated cytotoxic T cell upon herpes viruses infection. J Neuroinflammation. 2022;19(1):1-15.
| Files | ||
| Issue | Vol 22 No 1 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v22i1.12008 | |
| Keywords | ||
| Immune responses Herpes simplex virus-1 Viral infection | ||
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How to Cite
1.
Khodadoust MA, Keramatian GR, Kaffash Farkhad N, Tavakol-Afshari J. Investigating the Safety and Efficacy of the Synthetic Drug Herbix on Immune Responses Involved in the Treatment of a Mouse Model of Herpes Simplex Virus. Iran J Allergy Asthma Immunol. 2023;22(1):72-81.
