The herpes simplex virus (HSV) employs various mechanisms to evade the host immune response, significantly complicating treatment and prevention strategies. A pivotal study by Yao presents the cryogenic electron microscopy structure of the HSV-1 helicase-primase (HP) complex, revealing critical insights into its potential as a therapeutic target. The study elucidates the binding of clinically active small-molecule inhibitors, pritelivir and amenamevir, to the HP complex, providing a structural basis for the development of more effective antiviral agents (ref: Yao doi.org/10.1038/s41564-025-02168-4/). Concurrently, Roark's investigation into glycoprotein B (gB) highlights its role in HSV entry and immune evasion. The stabilization of the prefusion gB ectodomain allowed for the isolation of a neutralizing antibody, WS.HSV-1.24, which could enhance therapeutic strategies against HSV (ref: Roark doi.org/10.1038/s41564-025-02153-x/). Slein's research further underscores the importance of glycoproteins E and I in immune evasion, demonstrating that their interactions with the viral Fc receptor (vFcR) hinder antibody-mediated protection in neonatal HSV infections (ref: Slein doi.org/10.1126/scitranslmed.adu8579/). Zhou's work reveals how HSV-1 can circumvent type III interferon defenses in the cornea, facilitating its spread to the central nervous system, thus highlighting the virus's sophisticated immune evasion tactics (ref: Zhou doi.org/10.1016/j.celrep.2025.116581/). Lastly, Qu's findings on the alpha-herpesvirus US1 protein's interaction with cGAS illustrate another layer of immune suppression, as it inhibits type I interferon responses, further complicating the host's antiviral defense mechanisms (ref: Qu doi.org/10.1371/journal.ppat.1013669/).

Recent advancements in therapeutic approaches for herpes infections have focused on enhancing antiviral efficacy and developing novel delivery systems. Wang's study highlights the role of sphingomyelinase SMPDL3B in restricting cGAS-STING signaling during viral infections, suggesting that targeting this pathway could improve antiviral responses (ref: Wang doi.org/10.1016/j.immuni.2025.10.007/). Yao's earlier work on the HSV helicase-primase complex also contributes to this theme by providing structural insights that could guide the development of small-molecule inhibitors (ref: Yao doi.org/10.1038/s41564-025-02168-4/). Long's research introduces a novel approach using cholesterol surfactants to create biofunctional nanodiscs with antiviral properties, showcasing the potential of self-assembled lipid structures in drug delivery (ref: Long doi.org/10.1002/anie.202516207/). Zheng's identification of a macrocyclic peptide that suppresses STING-induced inflammation presents another innovative strategy to modulate immune responses in herpes infections (ref: Zheng doi.org/10.1016/j.ard.2025.10.023/). Strang's clinical data on valaciclovir's effectiveness in limiting vertical transmission of human cytomegalovirus (HCMV) during pregnancy underscores the importance of antiviral regimens in preventing congenital diseases (ref: Strang doi.org/10.1099/jgv.0.002178/). Finally, Castañeda Cataña's work on niosomes as nanocarriers for antiviral agents demonstrates the versatility of nanotechnology in enhancing drug delivery and efficacy (ref: Castañeda Cataña doi.org/10.1016/j.ijpharm.2025.126342/).

The interplay between various viral infections and co-infections presents significant challenges in understanding disease mechanisms and outcomes. Younis's study on Epstein-Barr virus (EBV) reveals its ability to reprogram autoreactive B cells into antigen-presenting cells, potentially driving autoimmunity in systemic lupus erythematosus (SLE) (ref: Younis doi.org/10.1126/scitranslmed.ady0210/). Muir's research investigates co-infections in northern koalas, identifying interactions between Chlamydia pecorum and various viruses, including phascolarctid herpesvirus and Koala retrovirus, which may influence disease severity and treatment responses (ref: Muir doi.org/10.1371/journal.ppat.1013632/). Kansou's case-control study highlights the impact of human papillomavirus (HPV) seminal carriage on virome diversity and male fertility, suggesting that viral co-infections could alter reproductive health outcomes (ref: Kansou doi.org/10.1186/s12958-025-01488-8/). Additionally, Wang's multicenter study on EBV detection in cerebrospinal fluid emphasizes the clinical relevance of viral presence in suspected intracranial infections, indicating potential diagnostic and therapeutic implications (ref: Wang doi.org/10.1016/j.ijid.2025.108235/). These studies collectively underscore the complexity of viral interactions and their implications for disease management.

The host immune response to herpes infections is a critical area of research, particularly in understanding latency and reactivation mechanisms. Yang's study on pseudorabies virus (PRV) demonstrates that pathogenic bacteria can trigger the transition from latency to reactivation, highlighting the role of co-infections in disease dynamics (ref: Yang doi.org/10.1126/sciadv.adw4206/). Monkhouse's investigation into the interaction between herpes simplex virus (HSV) protein pUL21 and protein phosphatase 1 reveals a non-canonical binding mechanism that may influence viral replication and immune evasion (ref: Monkhouse doi.org/10.1016/j.jbc.2025.110936/). Arbuckle's research on the H4K20-mono-methyltransferase SETD8 illustrates its role in modulating the accessibility of HSV genomes, suggesting that epigenetic factors are crucial in regulating viral latency and reactivation (ref: Arbuckle doi.org/10.1128/jvi.01293-25/). Strang's findings on valaciclovir's efficacy in reducing HCMV transmission during pregnancy further emphasize the importance of antiviral strategies in managing immune responses to herpes infections (ref: Strang doi.org/10.1099/jgv.0.002178/). Together, these studies provide insights into the intricate relationship between herpes viruses and host immune mechanisms.

Oncolytic viruses represent a promising avenue for cancer therapy, leveraging the selective targeting of cancer cells while sparing normal tissues. The exploration of viral interactions with the immune system is crucial for optimizing therapeutic outcomes. Rønnstad's systematic review assesses the effectiveness and safety of targeted therapies in atopic dermatitis, indirectly highlighting the potential of oncolytic viruses in modulating immune responses in cancer treatment (ref: Rønnstad doi.org/10.1007/s40257-025-00997-x/). Strang's work on valaciclovir's role in inhibiting HCMV replication during pregnancy also underscores the importance of antiviral strategies in cancer patients, particularly those with co-infections (ref: Strang doi.org/10.1099/jgv.0.002178/). Von Boxberg's research on humanized mouse models for EBV infection provides a platform for studying the oncogenic potential of herpesviruses, facilitating the development of targeted therapies (ref: von Boxberg doi.org/10.1002/cpz1.70257/). Zou's Mendelian randomization study suggests a unique association between COVID-19 and aplastic anemia, emphasizing the need for further investigation into the implications of viral infections on hematological health in cancer patients (ref: Zou doi.org/10.1186/s12967-025-07374-6/). Collectively, these studies highlight the intersection of virology and oncology, paving the way for innovative therapeutic strategies.

Understanding the epidemiology of herpesviruses is essential for public health strategies aimed at prevention and control. Zhao's randomized trial on the anti-CD38 monoclonal antibody CM313 in systemic lupus erythematosus emphasizes the need for targeted therapies in autoimmune conditions that may be influenced by herpesvirus infections (ref: Zhao doi.org/10.1038/s41392-025-02487-2/). Yuan's investigation into the anti-inflammatory properties of Leptocaramine from Hypecoum erectum highlights the potential of natural products in managing herpesvirus-related inflammation (ref: Yuan doi.org/10.1016/j.intimp.2025.115855/). Stefanizzi's prospective study on the safety and efficacy of the Recombinant Zoster Vaccine (RZV) in high-risk patients provides critical data on vaccination strategies for herpes zoster prevention, reinforcing the importance of immunization in public health (ref: Stefanizzi doi.org/10.1080/14760584.2025.2589216/). Strang's findings on valaciclovir's effectiveness in preventing congenital HCMV transmission further illustrate the significance of antiviral interventions in reducing the burden of herpesvirus-related diseases (ref: Strang doi.org/10.1099/jgv.0.002178/). These studies collectively underscore the importance of epidemiological research in informing public health policies and vaccination strategies.

Vaccine development for herpesviruses is a critical focus area, particularly in enhancing immune responses and preventing disease. Kouzeli's retrospective cohort study evaluates the impact of vaccination on shingles-related hospitalizations, providing valuable insights into the effectiveness of vaccination programs in older populations (ref: Kouzeli doi.org/10.1016/j.vaccine.2025.127951/). Stefanizzi's research on the safety and long-term protection offered by the Recombinant Zoster Vaccine (RZV) in high-risk patients further emphasizes the importance of vaccination in preventing herpes zoster and its complications (ref: Stefanizzi doi.org/10.1080/14760584.2025.2589216/). Strang's work on valaciclovir's role in reducing HCMV transmission during pregnancy highlights the need for effective antiviral strategies in vulnerable populations (ref: Strang doi.org/10.1099/jgv.0.002178/). These studies collectively underscore the importance of ongoing research in vaccine development and the need for robust immunization strategies to combat herpesvirus infections.