The Interplay of Genital Herpes with Cellular Processes: A Pathogenesis and Therapeutic Perspective

Abstract

Genital herpes, primarily caused by herpes simplex virus-2 (HSV-2), remains a pressing global health concern. Its remarkable ability to intertwine with cellular processes, from harnessing host machinery for replication to subverting antiviral defenses like autophagy and programmed cell death, exemplifies the intricate interplay at the heart of its pathogenesis. While the biomedical community has extensively researched antiviral interventions, the efficiency of these strategies in managing HSV-2 remains suboptimal. Recognizing this, attention has shifted toward leveraging host cellular components to regulate HSV-2 replication and influence the cell cycle. Furthermore, innovative interventional strategies-including drug repurposing, microbivacs, connecting the host microbiome, and exploiting natural secondary metabolites-are emerging as potential game changers. This review summarizes the key steps in HSV-2 pathogenesis and newly discovered cellular interactions, presenting the latest developments in the field, highlighting existing challenges, and offering a fresh perspective on HSV-2's pathogenesis and the potential avenues for its treatment by targeting cellular proteins and pathways.

Keywords: antivirals; genital herpes; herpes simplex virus-2; immune response; microbiome; vaccines.

Figure 1

HSV-2’s survival strategies and impact on host defense mechanisms: HSV-2 employs multiple strategies to persist and replicate, including latency in the trigeminal ganglion and periodic reactivation episodes. The virus disrupts cell death pathways, notably autophagy, to its advantage. Additionally, HSV-2 has the capability to induce aberrations in cell signaling and modify metabolic pathways.

Figure 2

Representative diagnostic methods for investigating HSV-2 infection: Several diagnostic techniques are employed to study HSV-2 infection. The gold standard for infectious virus detection is the plaque assay. Polymerase chain reaction (PCR) is utilized to identify viral genetic material. Electrophoresis is employed to detect both cellular and viral proteins. Immunofluorescence and histochemistry serve as valuable tools for pinpointing the cellular localization of viral particles.

Figure 3

Host microbiota and its dual impact following HSV-2 infection: The host microbiota exerts beneficial effects (A) by masking cell receptors and enhancing entry barriers; however, it can also have detrimental consequences (B) by disrupting membrane integrity and promoting the proliferation of anaerobic microflora after HSV-2 infection.

Figure 4

Diverse strategies for treating HSV-2 infection: Various approaches, including vaccines, drugs, nanomaterials, aptamers, and phytochemicals, have demonstrated effectiveness in preventing viral attachment, cell entry, and the release of mature virus. Additionally, gene editing can be harnessed to enhance the immune response and facilitate the development of antiviral vaccines.

Figure 5

Microbivac action: (A) HSV-2 infection in vaginal epithelial cells: Results in viral multiplication and disease progression. (B) ZOTENs as a microbivac against HSV-2: Functions by trapping the virus, leading to a substantial decrease in disease severity, enhanced antigen presentation, and an improved mucosal immune response.