Detection of the virulent neurotropic fungus Cladophialophora bantiana in clinical samples, primarily CNS tissue, increased four-fold in the period from 2023 to 2025.

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e276"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e277">Background:</h5> <p dir="auto" id="d48061961e279">Varicella-zoster virus (VZV) is a clinically important human neurotropic herpesvirus that causes varicella (chickenpox) as primary infection, typically in children. After primary infection, VZV establishes lifelong latency in sensory ganglia and can later reactivate and cause herpes zoster (shingles). Globally, varicella and shingles affect a substantial number of individuals each year. Although people with shingles can recover without specific antiviral treatment, the persistent, often severe pain associated with the disease can lead to depression and significantly decrease quality of life. Currently, acyclovir and its derivatives or similar compounds are the primary FDA-approved treatments for VZV infection. However, resistance to acyclovir, often because of mutations in the viral thymidine kinase, is increasingly observed in clinical settings. Therefore, alternative antiviral strategies against VZV are needed. Propolis (also known as “bee glue”), a resin-like substance produced by bees, has well-documented antibacterial and anti-inflammatory properties. Herein, we investigated the antiviral potential of propolis against VZV in in vitro systems including a cell culture model, human skin, and human dorsal root ganglia (DRG) tissue. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e281"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e282">Methods:</h5> <p dir="auto" id="d48061961e284">ARPE-19 cells, human fetal skin, DRG tissues, and the VZV pOka-Luc-GFP strain (expressing luciferase and GFP for viral monitoring) were used. Propolis (Brazilian green propolis in DMSO) cytotoxicity was assessed with MTT assays. Viral replication was quantified with time-dependent luciferase assays. RNA sequencing (RNA-seq) was performed to analyze differential gene expression in propolis-treated (0.0625% and 0.125%) and control cells (with/without VZV), and was followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Additionally, an acyclovir-resistant VZV mutant (VZV-delTK, lacking the thymidine kinase gene ORF36) was generated with BAC technology for a mechanistic comparison of propolis and acyclovir. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e286"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e287">Results:</h5> <p dir="auto" id="d48061961e289">MTT assays indicated that propolis at ≤0.125% had low cytotoxicity to ARPE-19 cells. Luciferase assays demonstrated that propolis inhibited VZV replication in a concentration-dependent manner. This efficacy was consistent in skin and DRG tissues, in which 0.1% propolis approached acyclovir’s antiviral activity. RNA-seq revealed that propolis altered host gene expression. Among the 207–1035 differentially expressed genes identified across concentrations, the enriched pathways included glycolysis/gluconeogenesis, calcium signaling, and ferroptosis. Propolis also inhibited VZV RNA transcription and splicing. Notably, propolis effectively inhibited the acyclovir-resistant strain VZV-delTK, whereas acyclovir did not, thus confirming the treatments’ distinct mechanisms. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e291"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e292">Conclusions:</h5> <p dir="auto" id="d48061961e294">Propolis exhibited significant antiviral activity against VZV in both cellular and tissue models, through a mechanism distinct from that of acyclovir. These results support further investigation of propolis as a potential anti-VZV agent with a novel mechanism of action. </p> </div>

Rabies virus (RABV) is a neurotropic virus of the genus Lyssavirus that causes a nearly always fatal encephalitis in humans once it reaches the central nervous system. Dog bites are a major transmissi...

Varicella zoster virus, the neurotropic herpesvirus behind chickenpox and shingles, has long been known to hide silently in sensory neurons after an initial infection, only to reawaken years later

Background: Global dementia cases, currently exceeding 55 million, are projected to triple by 2050. In the absence of disease-modifying therapies, identifying modifiable risk factors is critical. Preclinical studies show that herpes simplex virus type-1 (HSV-1) is neurotropic and can drive amyloid-beta accumulation and tau hyperphosphorylation. Epidemiologic findings remain inconsistent, partly because many studies lack standardized designs for real-world data. Objective: To quantify the association between clinically coded HSV-1 diagnosis and incident cognitive impairment or dementia among patients receiving care in a health-system electronic health record (EHR) network. Methods: We assembled a retrospective cohort within an Observational Medical Outcomes Partnership (OMOP)–mapped EHR data lake (2010‐2024), comparing patients with a first HSV-1 diagnosis (n=6274) to those without HSV-1 codes but with parallel baseline criteria (n=379,975). Eligibility required at least 365 days of prior observation and absence of baseline cognitive, HIV, selected neurotropic viral, or recent transplant codes. The outcome combined mild cognitive impairment and Alzheimer disease and related dementias (ADRD). A high-dimensional propensity score (PS) incorporating approximately 17,000 baseline covariates was estimated with regularized logistic regression; 4 strata weights were applied in a Cox model. Sensitivity analyses examined equipoise trimming, doubly adjusted models, fixed 1-, 5-, and 10-year censoring horizons, and a dementia-only outcome subset. Negative-control outcomes (n=271) were prespecified to assess empirical calibration. Results: The HSV-1 cohort contributed 23,186 person-years (PY) and 469 events; the non-HSV-1 cohort contributed 1,519,827 PY and 24,764 events. Crude incidence was 20.23 (95% CI 18.44‐22.14) per 1000 PY in the HSV-1 cohort and 16.29 (95% CI 16.09‐16.50) in the non-HSV-1 cohort, an absolute difference of 3.94 events per 1000 PY. PS-stratified analysis yielded a hazard ratio (HR) of 1.14 (95% CI 1.03‐1.25; =.007). Estimates were comparable after equipoise trimming (HR 1.12, 95% CI 1.01‐1.25, =.04), doubly adjusted modeling (HR 1.13, 95% CI 1.02‐1.24, =.01), and fixed 5-year (=.008) and 10-year follow-up (=.004) (both HR 1.15). The 1-year censored model showed HR 1.00 (95% CI 0.84‐1.20; =.96). The dementia-only endpoint mirrored the primary analysis (HR 1.14, 95% CI 1.03‐1.25; =.008). No postindex events occurred for any negative-control outcome, so empirical calibration could not be performed and all estimates are uncalibrated. Conclusions: Within an OMOP-standardized EHR cohort, an HSV-1 diagnosis was associated with a small elevation in the hazard of subsequent cognitive impairment or dementia compared with individuals with no recorded HSV-1 diagnosis. Given the ubiquity of HSV-1, even a modest elevation in individual hazard could translate to a meaningful population-level increment if the association is causal. Confirmation in external data sets with laboratory viral typing, antiviral treatment records, and mortality linkage is warranted.

Common, acute, non-neurotropic respiratory virus infections accelerate ALS disease progression well after the virus has been cleared by augmenting inflammation of glial cells in the spinal cord and mo...

UCL Discovery is UCL's open access repository, showcasing and providing access to UCL research outputs from all UCL disciplines.

<div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e276"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e277">Background:</h5> <p dir="auto" id="d48061961e279">Varicella-zoster virus (VZV) is a clinically important human neurotropic herpesvirus that causes varicella (chickenpox) as primary infection, typically in children. After primary infection, VZV establishes lifelong latency in sensory ganglia and can later reactivate and cause herpes zoster (shingles). Globally, varicella and shingles affect a substantial number of individuals each year. Although people with shingles can recover without specific antiviral treatment, the persistent, often severe pain associated with the disease can lead to depression and significantly decrease quality of life. Currently, acyclovir and its derivatives or similar compounds are the primary FDA-approved treatments for VZV infection. However, resistance to acyclovir, often because of mutations in the viral thymidine kinase, is increasingly observed in clinical settings. Therefore, alternative antiviral strategies against VZV are needed. Propolis (also known as “bee glue”), a resin-like substance produced by bees, has well-documented antibacterial and anti-inflammatory properties. Herein, we investigated the antiviral potential of propolis against VZV in in vitro systems including a cell culture model, human skin, and human dorsal root ganglia (DRG) tissue. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e281"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e282">Methods:</h5> <p dir="auto" id="d48061961e284">ARPE-19 cells, human fetal skin, DRG tissues, and the VZV pOka-Luc-GFP strain (expressing luciferase and GFP for viral monitoring) were used. Propolis (Brazilian green propolis in DMSO) cytotoxicity was assessed with MTT assays. Viral replication was quantified with time-dependent luciferase assays. RNA sequencing (RNA-seq) was performed to analyze differential gene expression in propolis-treated (0.0625% and 0.125%) and control cells (with/without VZV), and was followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Additionally, an acyclovir-resistant VZV mutant (VZV-delTK, lacking the thymidine kinase gene ORF36) was generated with BAC technology for a mechanistic comparison of propolis and acyclovir. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e286"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e287">Results:</h5> <p dir="auto" id="d48061961e289">MTT assays indicated that propolis at ≤0.125% had low cytotoxicity to ARPE-19 cells. Luciferase assays demonstrated that propolis inhibited VZV replication in a concentration-dependent manner. This efficacy was consistent in skin and DRG tissues, in which 0.1% propolis approached acyclovir’s antiviral activity. RNA-seq revealed that propolis altered host gene expression. Among the 207–1035 differentially expressed genes identified across concentrations, the enriched pathways included glycolysis/gluconeogenesis, calcium signaling, and ferroptosis. Propolis also inhibited VZV RNA transcription and splicing. Notably, propolis effectively inhibited the acyclovir-resistant strain VZV-delTK, whereas acyclovir did not, thus confirming the treatments’ distinct mechanisms. </p> </div><div xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" class="section"> <a class="named-anchor" id="d48061961e291"> <!-- named anchor --> </a> <h5 class="section-title" id="d48061961e292">Conclusions:</h5> <p dir="auto" id="d48061961e294">Propolis exhibited significant antiviral activity against VZV in both cellular and tissue models, through a mechanism distinct from that of acyclovir. These results support further investigation of propolis as a potential anti-VZV agent with a novel mechanism of action. </p> </div>