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Herpes Simplex Virus: Immunity, Pathogenicity, Immune Escape Mechanisms, and Antiviral Strategies

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 2109

Special Issue Editor

Prof. Dr. Maria Teresa Sciortino

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, Italy
Interests: immunological aspects of herpesvirus infections; role of PCD in pathogenesis of viral infections; functional studies of UL49 and UL41 structural proteins, during HSV replication; involvement of ERK1 pathway in the modulation of CCR5 receptor; studies of cyclodextrins carriers as drug or nucleic acid delivery system for cancer therapy, imaging and for antiviral treatment
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Special Issue Information

Dear Colleagues,

The Herpes Simplex Virus (HSV) represents a significant global health challenge due to its ability to establish lifelong latency, evade the host immune system, and cause various diseases, from mild skin infections to severe neurological disorders. This Special Issue aims to consolidate current research on the intricate interplay between HSV and the host immune system, focusing on the epigenetic mechanisms regulating HSV infection and latency, as well as exploring the multifaceted roles of tegument proteins to identify the molecular mechanisms underlying HSV pathogenesis and facilitate the development of novel antiviral strategies. Through this comprehensive approach, this Special Issue seeks to advance our understanding of HSV biology and contribute to the development of more effective therapeutic interventions.

Prof. Dr. Maria Teresa Sciortino
Guest Editor

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Keywords

  • herpes simplex virus (HSV)
  • latency
  • immune evasion
  • tegument proteins
  • epigenetic mechanisms
  • viral pathogenesis
  • antiviral strategies
  • molecular mechanisms
  • therapeutic interventions

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Published Papers (2 papers)

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Research

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18 pages, 25244 KB  
Article
The Procaine-Based ProcCluster® Impedes the Second Envelopment Process of Herpes Simplex Virus Type 1
by Johannes Jungwirth, Lisa Siegert, Lena Gauthier, Andreas Henke, Oliver H. Krämer, Beatrice Engert and Christina Ehrhardt
Int. J. Mol. Sci. 2025, 26(15), 7185; https://doi.org/10.3390/ijms26157185 - 25 Jul 2025
Viewed by 678
Abstract
Herpes simplex virus type 1 (HSV-1) has a global prevalence of 64%. Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new [...] Read more.
Herpes simplex virus type 1 (HSV-1) has a global prevalence of 64%. Established antiviral drugs, such as acyclovir (ACV), have been successfully used over the past decades. However, due to growing viral resistance against approved antivirals and the lack of effective vaccines, new concepts are essential to target HSV-1 infections. Here, we present data on the inhibitory effect of the procaine-based substance ProcCluster® (PC) in reducing HSV-1 replication in vitro. Non-toxic PC concentrations significantly decreased HSV-1 replication in infected cells. Immunofluorescence microscopy revealed an accumulation of viral proteins in early and recycling endosomes, resulting in reduced viral release. The combination of PC with ACV resulted in an enhanced antiviral effect. Based on these results, PC alone, as well as in combination with ACV, appears to be a promising substance with antiviral potential against HSV-1 infections. Full article
(This article belongs to the Special Issue Herpes Simplex Virus: Immunity, Pathogenicity, Immune Escape Mechanisms, and Antiviral Strategies)
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Review

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16 pages, 1541 KB  
Review
Topical and Systemic Therapeutic Approaches in the Treatment of Oral Herpes Simplex Virus Infection: A Systematic Review
by Antonio Mancini, Angelo Michele Inchingolo, Grazia Marinelli, Irma Trilli, Roberta Sardano, Carmela Pezzolla, Francesco Inchingolo, Andrea Palermo, Gianna Dipalma and Alessio Danilo Inchingolo
Int. J. Mol. Sci. 2025, 26(17), 8490; https://doi.org/10.3390/ijms26178490 - 1 Sep 2025
Viewed by 992
Abstract
Herpes Simplex Virus (HSV) infections, caused primarily by HSV-1 and HSV-2, are among the most prevalent viral diseases worldwide, with recurrent manifestations that significantly affect quality of life. Therapeutic strategies include both topical and systemic interventions, each with distinct goals. This systematic review [...] Read more.
Herpes Simplex Virus (HSV) infections, caused primarily by HSV-1 and HSV-2, are among the most prevalent viral diseases worldwide, with recurrent manifestations that significantly affect quality of life. Therapeutic strategies include both topical and systemic interventions, each with distinct goals. This systematic review was conducted according to PRISMA guidelines. A comprehensive search of PubMed, Scopus, and Web of Science (2005–2025) identified studies evaluating topical or systemic treatments for HSV. Eligible studies included randomized controlled trials and observational studies reporting validated clinical outcomes. Topical treatments, including acyclovir cream, docosanol, and newer formulations, primarily reduce lesion duration and alleviate local symptoms when applied early. These interventions have limited systemic absorption and generally do not influence recurrence frequency. Novel delivery methods and combination strategies, such as acyclovir–hydrocortisone formulations or photodynamic therapy, may enhance local efficacy and symptom control. Systemic Therapies: Systemic antivirals, such as acyclovir, valacyclovir, and famciclovir, target both lesion resolution and recurrence prevention. Evidence from randomized trials supports their use for episodic and suppressive therapy, including short-course, high-dose regimens that improve adherence while controlling symptoms. Systemic therapy is particularly indicated for recurrent, disseminated, or high-risk infections. Topical and systemic therapies serve complementary roles in HSV management. Topical agents are useful for localized or initial episodes, while systemic therapy addresses broader clinical objectives, including recurrence reduction. Future research should focus on mechanism-based therapies, novel delivery systems, and standardized outcome measures to guide personalized treatment strategies. Emerging therapies targeting viral latency, immune modulation, and gene-editing technologies hold promise for long-term suppression and personalized management of HSV infections. Full article
(This article belongs to the Special Issue Herpes Simplex Virus: Immunity, Pathogenicity, Immune Escape Mechanisms, and Antiviral Strategies)
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