Oncolytic herpes simplex virus (HSV) therapies are emerging as promising treatments for various cancers, particularly those resistant to conventional therapies. A pooled analysis of multicenter studies evaluated the safety and efficacy of VG161, a multiarmed oncolytic HSV-1 expressing interleukin (IL)-12, IL-15, and a PD-L1 antagonist, in patients with intrahepatic cholangiocarcinoma (ICC). The study demonstrated that VG161 not only induced tumor regression but also elicited significant immunological responses, highlighting its potential as a novel therapeutic option for advanced ICC (ref: Shen doi.org/10.1136/gutjnl-2025-335904/). Another study explored the combination of talimogene laherparepvec (T-VEC) with isolated limb perfusion (ILP) for melanoma and sarcoma, reporting a 53% overall response rate, which underscores the synergistic effects of oncolytic virotherapy and immune checkpoint inhibition (ref: Hayes doi.org/10.1136/jitc-2025-012446/). Furthermore, Tuyaerts et al. demonstrated that an oncolytic HSV-1 engineered to express FLT3L effectively killed melanoma, glioblastoma, and pancreatic cancer cells, suggesting that the incorporation of immune-stimulatory transgenes can enhance the therapeutic efficacy of oncolytic viruses (ref: Tuyaerts doi.org/10.1016/j.omton.2025.201031/). Collectively, these studies illustrate the multifaceted roles of oncolytic HSV therapies in activating antitumor immunity and their potential to improve patient outcomes in various malignancies.

The mechanisms underlying herpes simplex virus (HSV) pathogenesis are complex and involve various host interactions. Du et al. provided insights into the role of the actin cytoskeleton in HSV-1 endocytic uptake and membrane fusion, revealing that actin dynamics are crucial for viral entry (ref: Du doi.org/10.1021/acsnano.5c09935/). In a related study, Liu identified the tegument protein VP22 of pseudorabies virus as a viral antagonist of the type I interferon response, demonstrating how viral proteins can disrupt host immune defenses by targeting cellular components like DDX21 (ref: Liu doi.org/10.1371/journal.ppat.1013549/). Additionally, Cattaneo's research highlighted the implications of genetic mutations in HSV-1 replication-defective vectors for gene therapy applications, emphasizing the need to understand HSV-1 interactions with neural tissues to harness its potential for therapeutic use (ref: Cattaneo doi.org/10.1038/s41434-025-00566-1/). These findings collectively enhance our understanding of HSV pathogenesis and suggest potential therapeutic strategies that could exploit these viral mechanisms.

Epstein-Barr virus (EBV) is implicated in various malignancies, and recent studies have elucidated its interactions with environmental factors and host genetics. Michailidis et al. investigated the effects of aflatoxin B1, a dietary carcinogen, on histone modifications in EBV-infected Burkitt lymphoma cells, revealing that combined exposure leads to significant epigenetic alterations (ref: Michailidis doi.org/10.1016/j.envint.2025.109813/). Furthermore, Jing's study on EBV-associated smooth muscle tumors highlighted the heterogeneous immune statuses and novel pathogenic mutations in affected patients, expanding the understanding of EBV's role in tumorigenesis (ref: Jing doi.org/10.1111/his.15558/). Cederberg's prospective study on primary EBV infection in preadolescent children provided critical insights into the natural history of EBV, emphasizing its potential as a precursor to several cancers and autoimmune disorders (ref: Cederberg doi.org/10.1016/j.jcv.2025.105859/). These studies underscore the multifactorial nature of EBV-associated cancers and the need for further research into their pathophysiology.

Cytomegalovirus (CMV) remains a significant concern in immunocompromised populations, and recent studies have focused on its impact on immune responses and treatment strategies. Chow et al. demonstrated that letermovir is well tolerated and effective for primary CMV prophylaxis after heart transplantation, showing no episodes of neutropenia compared to historical controls (ref: Chow doi.org/10.1016/j.healun.2025.08.023/). Additionally, Baruah's research identified the activation of the BTK-DDX41-STING signaling axis during lytic CMV infection, which plays a crucial role in protective interferon responses (ref: Baruah doi.org/10.1128/jvi.01048-25/). Li's study on human herpesvirus 6B revealed its ability to suppress interferon production, highlighting the immune evasion strategies employed by herpesviruses (ref: Li doi.org/10.1128/jvi.00984-25/). Collectively, these findings emphasize the importance of understanding CMV's interactions with the immune system to develop effective therapeutic strategies.

Herpes zoster (shingles) vaccination is critical for preventing this painful condition, particularly in at-risk populations. Wang et al. conducted a phase 3 clinical trial evaluating a live-attenuated herpes zoster vaccine in Chinese adults aged 40 years and older, demonstrating its efficacy and safety in reducing the incidence of herpes zoster (ref: Wang doi.org/10.1016/j.cmi.2025.09.009/). In a cohort of people living with HIV, Arsuffi's study assessed the prevalence of herpes zoster reactivation post-vaccination with a recombinant vaccine, finding a significant reduction in cases compared to pre-vaccination rates (ref: Arsuffi doi.org/10.1016/j.vaccine.2025.127723/). Mizuno's research further explored the association between shingles and COVID-19, revealing elevated incidence rates of herpes zoster following COVID-19 infection, which raises concerns about the potential impact of viral infections on zoster reactivation (ref: Mizuno doi.org/10.1093/ije/). These studies collectively highlight the importance of vaccination in mitigating the risks associated with herpes zoster, particularly in vulnerable populations.

Viral infections can have profound neurological implications, particularly concerning the integrity of the blood-brain barrier (BBB). Boardman et al. reviewed the mechanisms by which various viral infections, including HSV and SARS-CoV-2, compromise BBB integrity, leading to neurological complications (ref: Boardman doi.org/10.1093/infdis/). Additionally, Chasseur's study identified virus-derived circular RNAs that play roles in oncogenesis and viral fitness, suggesting that these non-coding RNAs may also influence neurological outcomes (ref: Chasseur doi.org/10.1371/journal.ppat.1013448/). The interplay between viral infections and host immune responses, as highlighted by Collercandy's research on Vα1 T cells in the context of HIV-1 persistence, further complicates the landscape of viral-induced neurological disorders (ref: Collercandy doi.org/10.1371/journal.ppat.1013489/). These findings underscore the need for a comprehensive understanding of viral pathogenesis to develop effective therapeutic interventions for neurological complications.

The development of antiviral drugs for herpes simplex virus (HSV) is critical due to the challenges posed by drug resistance. Andreu's study introduced a novel endonuclease inhibitor inspired by baloxavir that effectively prevents HSV-1 replication in vitro and in vivo, showcasing its potential as a new therapeutic option (ref: Andreu doi.org/10.1002/advs.202508006/). Mofed's research highlighted the role of CCL2 in modulating viral budding and replication, indicating that targeting host factors may provide alternative strategies to combat viral resistance (ref: Mofed doi.org/10.1128/mbio.02241-25/). Furthermore, the prevalence of bacterial vaginosis among South African adolescent girls and its association with STIs, including HSV, emphasizes the need for integrated approaches to address viral infections and their complications (ref: Mbulawa doi.org/10.1007/s15010-025-02649-y/). Together, these studies reflect the ongoing efforts to develop innovative antiviral therapies and address the challenges of resistance.

Viral interactions with host immune systems are critical for understanding viral pathogenesis and developing effective therapies. Lee et al. provided structural insights into how various viral inhibitors, including those from herpesviruses, target the antigen transporter TAP, thereby evading immune detection (ref: Lee doi.org/10.1073/pnas.2516676122/). Additionally, Baruah's study on the activation of the BTK-DDX41-STING axis during CMV infection highlights the importance of innate immune signaling in combating viral infections (ref: Baruah doi.org/10.1128/jvi.01048-25/). Ng's evaluation of CMV cell-mediated immunity assays underscores the challenges of validating immune response tests in diverse populations, emphasizing the need for tailored approaches to monitor and enhance immune responses against viral infections (ref: Ng doi.org/10.1016/j.jcv.2025.105858/). These findings collectively illustrate the intricate dynamics between viruses and host immune systems, paving the way for novel therapeutic strategies.