Search Results (492)

Herpesvirus infections belong to major pathogens in the human population. This study aimed at evaluating diagnostic data for eight human herpesviruses, based on datasets derived from a large European tertiary care center. Specifically, we analyzed 118,692 herpesvirus submittals to the Diagnostic Division of the Virological Institute, University Hospital Erlangen (UKER), Germany, between July 2014 and June 2024. Our points of focus were the following: (i) the frequencies of herpesvirus diagnostic results with positivity rates, (ii) departments representing main sample submitters, (iii) the specific importance of intensive care units (ICUs), (iv) the COVID-19 pandemic period, and (v) distinct properties of sample types. Overall, we are stating the highest frequencies of diagnostic assessment for herpes simplex virus (HSV), human cytomegalovirus (HCMV), and Epstein–Barr virus (EBV) infections, pointing to their dominant relevance for clinical practice. Notably, HCMV submittals (46.6% of total), together with EBV (26.2%) and HSV (15.7), accounted for almost 90% of all herpesviral diagnostic samples during this period. Within these key groups, HCMV, EBV and HSV showed positivity rates of 14.5%, 35.0%, and 18.5%, respectively. Concerning a main input of sample submittals, two departments were predominant in our center, i.e., the Departments of Haematology–Oncology and Anaesthesiology. These included patients under multifold types of treatment associated with an increased risk of herpesvirus reactivation or primary infection. Furthermore, another high portion of submittals was noted for ICUs and external sources. In addition, a numerical, transient increase in herpesvirus diagnostic submittals, from various sources, was shown for the COVID-19 pandemic years (mostly 2021) as compared to other periods. Combined, these data underlined the importance of clinical monitoring of herpesvirus infections, particularly for high-risk patients, and the steady need of improvements in preventive measures, therapeutic options, and safe diagnostic tools. Full article

Three species of suid herpesviruses (SuHVs) have been reported in pigs, specifically pseudorabies virus (PRV), porcine cytomegalovirus (PoCMV), and porcine lymphotropic herpesvirus (PLHV). However, their genetic diversity and epidemic circulating status in China remain largely unclear. In this study, 7200 nasal swabs and 2571 serum samples were collected from pigs across 17 provincial regions in China in 2017. All samples were pooled into 22 libraries based on sample type and geographic origin for high-throughput next-generation sequencing. Metaviromic analysis identified all three SuHV species, revealing marked variations in their detection rates and viral abundance. Notably, PoCMV and PRV were detected in all 17 sampled provinces, accompanied by high viral genome sequence abundance (RPM > 1 × 10²), while PLHV was only found in nasal swabs from 10 provinces, with extremely low sequence abundance (RPM < 2). Further phylogenetic and genetic diversity analyses revealed notable molecular characteristics of the three circulating SuHVs: PoCMV exhibited substantial genetic diversity with at least two major evolutionary clades identified in Chinese pig populations; variant genotype II PRV strains were confirmed as the predominant circulating lineage; and potential PLHV variants with partial sequence divergence from the reference strain were also found to circulate in China. These findings enrich the molecular epidemiological data of SuHVs in Chinese pig populations and highlight the previously overlooked, highly widespread circulation of PoCMV, warranting attention to its potential impacts on swine health and production performance. Full article

Marine seaweeds are recognized as a rich source of structurally diverse bioactive compounds, particularly sulfated polysaccharides with promising biomedical applications. In the present study, a sulfated polysaccharide Codium tomentosum fraction (PSCT) was extracted from the Moroccan green seaweed Codium tomentosum and subjected to comprehensive chemical, structural, and biological characterization. The extraction yield reached 22.01%, and the polysaccharide fraction was mainly composed of neutral sugars (66.84%), along with significant levels of sulfate groups (8.73%) and uronic acids (4.13%). Monosaccharide analysis revealed a predominance of galactose and arabinose, indicating a complex heteropolysaccharide structure. Spectroscopic and morphological analyses (FTIR, XRD, UV–Vis, and SEM–EDS) suggested predominantly amorphous characteristics and confirmed the sulfated profile of the extract. Biological evaluation demonstrated that PSCT exhibits multifunctional bioactivities. The extract showed notable antiviral activity against Herpes Simplex Virus 1 (HSV1), with an EC₅₀ value of 12.22 ± 2.90 µg/mL and no detectable cytotoxicity (CC₅₀ > 200.00 µg/mL). In addition, PSCT displayed strong antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Candida albicans, with remarkably low MIC values ranging from 0.05 to 0.78 mg/mL. Furthermore, antioxidant assays revealed concentration-dependent activity, with up to 68% DPPH radical scavenging and an IC₅₀ of 1.25 mg/mL, indicating a moderate antioxidant potential, along with notable reducing power in the FRAP assay. Overall, these findings highlight the potential of C. tomentosum-derived polysaccharides as multifunctional natural agents with antiviral, antimicrobial, and antioxidant properties, supporting their prospective application in pharmaceutical and biomedical fields. Full article

The rectal mucosa houses a large number of viruses with important roles in shaping the local microbial communities and modulating immune responses, which could influence host susceptibility to infection and other diseases. Unique composition of the gut microbiome, including the predominance of clinically significant eukaryotic viruses like herpesviruses, cytomegalovirus, and human papillomavirus, has been described in both people with HIV (PWH) and men who have sex with men (MSM) vulnerable to HIV. Despite these insights, the rectal virome and the clinical implications of virome–bacteriome–immune interactions in the rectal mucosa remain poorly understood. In this review, we synthesize existing data on the composition of the rectal virome, its interactions with the bacteriome and the immune system, and implications on clinical outcomes in people living with or vulnerable to HIV. We also highlight the gaps and research needed to further explore and unravel these relationships. Full article

The presence of human herpesviruses is frequently detected in the oral cavity, yet their disease-specific role in chronic inflammatory oral mucosal disorders remains uncertain. This comparative observational study investigated Epstein–Barr virus (EBV) and human herpesvirus-7 (HHV-7) genomic sequences in saliva and virus-specific antibodies in serum among patients with oral lichen planus (OLP; n = 35), aphthous stomatitis (AS; n = 31), and healthy controls (n = 34). Salivary viral loads were quantified using real-time PCR, while EBV and HHV-7-specific IgG and IgM antibodies were measured using ELISA-based assays. EBV and HHV-7 DNA in saliva were commonly detected across all groups, demonstrating high baseline shedding and marked interindividual variability. Although EBV IgG levels were higher in OLP compared with AS in univariate analysis, multivariate regression revealed that age, rather than disease status, was the primary determinant of EBV IgG levels. After adjustment for age, sex, and discomfort, neither EBV nor HHV-7 salivary loads showed independent associations with OLP or AS. HHV-7 salivary loads were uniformly distributed among groups. These findings suggest that salivary detection of EBV and HHV-7 reflects widespread latent infection rather than disease-specific activity in OLP or AS. Longitudinal and tissue-based studies integrating immunological profiling are warranted to clarify whether herpesvirus reactivation contributes to disease severity in defined patient subgroups. Full article

Elaeocarpus sylvestris (Lour.) Poir., an evergreen tree native to East and Southeast Asia, has gained increasing scientific attention owing to its broad pharmacological properties. Traditionally used in East Asian medicine to treat inflammation, fever, and infectious diseases, modern research has revealed diverse bioactivities, including potent antioxidant, anti-inflammatory, antiviral, anticancer, antidiabetic, and immunomodulatory effects. This therapeutic potential is primarily attributed to its rich phytochemical composition, particularly polyphenols such as geraniin, 1,2,3,4,6-penta-O-galloyl-β-D-glucose and quercetin. This review particularly focuses on the chemistry of E. sylvestris, summarizing structurally elucidated compounds, including hydrolysable tannins, flavonoids, and triterpenoids, along with recent insights into the structure–activity relationships that underpin these antiviral, antioxidant, and anticancer activities. Recent studies have demonstrated substantial antiviral efficacy of E. sylvestris extracts and isolated compounds against major human pathogens, including herpesviruses, influenza A virus, and SARS-CoV-2, supported by in silico, in vitro, in vivo, and early-phase clinical evaluations. Its cosmeceutical applications, including antioxidant, skin-whitening, and blue-light protective effects, further highlight its multifunctional potential. To our knowledge, this is the first comprehensive review summarizing the phytochemistry, pharmacological activities, therapeutic potential, and cosmeceutical applications of E. sylvestris. Despite these promising findings, challenges remain in elucidating precise molecular mechanisms, pharmacokinetics, and clinical validation. This review identifies current research gaps and future directions necessary to advance E. sylvestris as a scientifically validated natural therapeutic resource. Full article

Background: Herpes simplex virus (HSV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) establish lifelong latency in sensory neurons, lymphoid tissue, and myeloid–endothelial cells, respectively. A substantial proportion of adults worldwide are infected with all three viruses and may experience concurrent herpesvirus latency, yet they have largely been studied independently. This review examined whether latent and intermittently reactivating herpesviruses share overlapping inflammatory signatures and whether their combined presence contributes to chronic inflammatory burden. Methods: A narrative integrative review was conducted using MEDLINE, Embase, and Google Scholar (inception–October 2025). Evidence from thirty-one cohort studies and mechanistic investigations spanning virology, immunology, neurology, and clinical medicine was synthesized. Results: Herpesvirus reactivation rates ranged from 23% in general Intensive Care Unit (ICU) populations to 85% in severe COVID-19. Concurrent reactivation of multiple viruses occurred in 34–63% of critically ill patients and was associated with worse clinical outcomes. Notably, simultaneous CMV and EBV reactivation independently predicted mortality (adjusted hazard ratio, 3.17; 95% CI, 1.41–7.13). Across infections, overlapping inflammatory biomarkers, including IL-6, TNF-α, CRP, and PGE₂, were consistently elevated, reflecting convergent activation of IFN and NF-κB signaling pathways. Mechanistic studies suggest cross-compartment immune priming, where CMV-driven T-cell exhaustion facilitates EBV reactivation, and viral cytokine signaling enhances HSV-associated neuroinflammation. Conclusions: HSV, EBV, and CMV triple latency may represent an underrecognized contributor to chronic inflammation in immunocompetent hosts. Understanding this multi-virus inflammatory network may inform mechanistic research, biomarker-guided risk stratification, and therapeutic strategies targeting convergent inflammatory pathways. Prospective interventional studies incorporating concurrent multi-virus monitoring are needed to clarify causal relationships. Full article

Glioblastoma is the most aggressive tumor among gliomas, and recurrence remains inevitable despite aggressive therapies. Resistance to existing treatment modalities is attributed in part to the presence of glioma stem cells, which comprise a distinct cell subpopulation that sustains cell renewal and tumor evasion through multiple mechanisms. Therapeutic strategies using herpesviruses have been evaluated following the discovery of differential human cytomegalovirus (HCMV) expression in glioblastoma tumor cells. The absence of expression in normal brain tissue led to multiple clinical trials demonstrating the potential clinical utility of targeted HCMV via herpesvirus-based oncolytic therapeutic strategies. This review provides a comprehensive overview of existing studies evaluating the expression and biological significance of HCMV within glioma stem cells. Targeting HCMV in this cellular compartment may disrupt the continuous cellular support and resilience of glioblastoma stem cells, thereby enhancing the efficacy of current treatments. Full article

The order Herpesvirales contains three families, Orthoherpesviridae, Alloherpesviridae, and Malacoherpesviridae. The time since divergence of families from the common ancestor makes protein primary sequence comparison an insensitive tool for identifying common genes. Comparison of three-dimensional protein structures can reveal similarities that are not evident in primary sequences. Salmonid herpesvirus 1 (SalHV-1) is an alloherpesvirus. Complete sequencing of SalHV-1 VR-868 strain Winthrop by a combination of short- and long-read methods revealed 120 putative open reading frames (ORFs). BLAST search for similar protein sequences discovered five ORFs that encoded proteins with homologs in the orthoherpesviruses, including the major capsid protein, capsid triplex subunit 2, the catalytic subunit of the DNA polymerase, the helicase subunit of the helicase/primase complex, and the terminase ATPase subunit. An annotation of the ORFs of SalHV-1 was performed in which ORFs of SalHV-1 were modeled using AlphaFold3, and the models were used as prompts for structural similarity search using DALI and FoldSeek. Completion of this search strategy for the entire genome expanded the set of genes shared among the Herpesvirales to include additional proteins related to DNA replication and genome integrity, capsid assembly and genome packaging, and capsid nuclear egress. No homologs for any tegument proteins or proteins of the conserved entry apparatus of the Herpesviridae (gB, gH or gL) were discovered. Full article

Caprine herpesvirus 1 (CpHV-1) is responsible for significant economic losses in goat farming. The CpHV-1 genital infection in goats has been used as a homologous animal model for the study of human herpes simplex virus type 2 (HSV-2). This study aimed to investigate the in vitro virucidal and antiviral effect of lemon juice (LJ) and its main component, citric acid (CA), against CpHV-1 on Madin-Darby Bovine Kidney (MDBK) cells. Cytotoxicity was assessed using an XTT assay, while viral titers were determined by the Reed–Muench method and viral DNA was quantified via qPCR. Pure LJ (pH 2.3) and its corresponding CA solution demonstrated potent and rapid virucidal activity, reducing the viral titer by over 5.0 log10 TCID₅₀/50 µL within 1 min. When applied after viral entry, a non-cytotoxic dilution of LJ (pH 4.32) significantly inhibited viral replication, causing a 2.5 log10 TCID₅₀/50 µL reduction in viral titer and a corresponding decrease in viral DNA. The antiviral effects were minimal at a near-neutral pH of 6.67, probably interacting with envelope structures. These results suggest that LJ could be a potential low-cost topical agent or disinfectant for controlling CpHV-1 in goat populations and offer a basis for translational research on human herpesviruses. Full article

Background: Members of the virus family Herpesviridae are among the most successful pathogen groups in evolutionary history. They not only pose a serious public health threat to humans but also cause significant economic losses in the global livestock industry. The primary immunological challenge in developing sterilizing vaccines is the lifelong latency of herpesviruses in the nervous system or lymphoid tissues. Methods: This analysis compares the vaccine strategies designed against the five most important Alphaherpesvirinae pathogens: HSV-1/2, PRV, BHV-1, EHV-1/4, and FHV-1. The contrast between the globally licensed veterinary vaccines and the relative stagnation in the field of human HSV vaccines is stark. However, there are notable success stories regarding the implementation of ‘Marker Vaccines’ (DIVA strategies) in veterinary medicine. This review examines various vaccine modalities, assessing their potential to mitigate clinical outbreaks and their shortcomings in preventing viral shedding and establishing latency. Results: This study reveals common technical bottlenecks across species, attributed to immune evasion mechanisms such as the downregulation of MHC I, TAP inhibition, the failure to induce robust mucosal IgA, and safety concerns regarding the recombination of live vectors. Conclusions: This review highlights several promising avenues that could lead to enhanced herpesvirus vaccines and recommends the rational design of T-cell epitopes alongside innovative mucosal adjuvants. Furthermore, it bridges the gap between veterinary and human vaccinology from a One Health perspective, suggesting that lessons learned from veterinary practices could facilitate necessary breakthroughs in human medicine. Full article

Amphibian populations are undergoing dramatic global declines, with infectious diseases recognized as major contributors. While chytridiomycosis, caused by Batrachochytrium dendrobatidis (Bd), and disease caused by ranaviruses are well known, herpesviruses in amphibians remain comparatively neglected. We conducted a passive survey using carcasses collected between 2022 and 2025 in Schleswig-Holstein, northern Germany. Dead amphibians (n = 187) were dissected. Skin, kidney, liver, and brain samples were screened for Bd, ranaviruses, bufonid herpesvirus 1 (BfHV1), and ranid herpesvirus 3 (RaHV3) by PCR. BfHV1 was detected in nearly half of the Bufo bufo (common toads; 48.6%), while RaHV3 was identified in 23.6% of the Rana temporaria (common frogs) examined. Bd was detected in a single B. bufo, while ranaviruses were not detected. BfHV1 was present in skin, liver, kidney, and brain samples, whereas RaHV3 was detected exclusively in skin samples. No macroscopical or histological lesions characteristic of herpesviruses or Bd were found. However, the carcass-based approach frequently limited detailed examination due to compromised sample quality. Our findings confirm the presence of amphibian herpesviruses (BfHV1 and RaHV3) in the region without associated lesions, raising questions about their potential to cause systemic infections. Furthermore, our results highlight the limitations of carcass-based surveillance and underscore the need for complementary diagnostic approaches, such as immunohistochemistry and meta-omics. Full article

Here we discuss three veterinary alphaherpesviruses—pseudorabies virus, equid alphaherpesvirus 1, and bovine alphaherpesvirus 1—that were instrumental in uncovering the true extent of transcriptome complexity through long-read RNA sequencing, which earlier short-read approaches could not resolve. We focus on three major transcriptomic features whose discovery and characterization relied heavily on these viral models: (i) widespread transcriptional overlaps that complicate read assignment and may drive transcriptional interference; (ii) diverse transcript isoforms arising from alternative 5′ and 3′ transcript termini, as well as splicing; and (iii) non-coding RNAs clustered near replication origins that illuminate potential replication–transcription interactions on a shared nuclear template. Long-read viromics in these veterinary systems has additionally served as a stringent benchmark for transcript callers and annotation pipelines, because the extreme density of overlaps and co-terminal transcript families exposes errors that often go unnoticed in typical mammalian transcriptomes. This has made veterinary herpesvirus datasets disproportionately influential in shaping best practices for full-length isoform calling, transcript end mapping, and artifact-robust cDNA library handling. We also discuss animal gammaherpesviruses as proxies for human gammaherpesviruses, allowing experimental investigation of viral programs difficult to study in human infection. Finally, we describe pseudorabies virus applications as a retrograde transneuronal tracer. Full article

Viral helicases are conserved nucleic acid-dependent ATPases that drive genome replication, gene expression, and virion assembly, thereby playing a central role in viral replication and pathogenicity. Here, we discuss structural, biochemical, and virological data to compare helicase superfamilies, their conserved motifs, and translocation models that couple ATP hydrolysis to strand separation. We then analyze how viral helicases regulate replication fork progression, transcription and translation of viral RNAs, viral genome remodeling during replication, genome-packaging strategies, and evasion of innate immune signaling. Mechanistic examples from picornaviruses, flaviviruses, herpesviruses, and coronaviruses demonstrate how helicase architecture, substrate specificity, and cofactors control these activities. Finally, we discuss the opportunities and drawbacks of targeting viral helicases with antiviral drugs, recent screening and structure-guided discovery efforts, and emerging resistance mechanisms. Overall, this review provides a virus-centered synthesis of helicase structure, function, and inhibition that links conserved enzymatic activities to diverse infection outcomes and antiviral strategies across viral families. Full article

Human herpesviruses (HHVs) are notorious, ubiquitous intracellular pathogens that establish lifelong infections in the host. They tightly manipulate host signaling pathways that play central roles in key cellular processes such as cell survival, metabolism, immune responses, and oncogenic transformation. Among the many pathways explored, the phosphatidylinositol-3-kinase (PI3K)/Akt signaling axis has emerged as a central and conserved target exploited by all eight HHVs. Herpesviruses can induce PI3K/Akt signaling at multiple stages of their life cycle, beginning at viral entry and extending through lytic replication, latency maintenance, immune evasion, and virus-associated tumorigenesis. Mechanistically, herpesviruses engage both host cell receptors and viral effector proteins to activate PI3K, drive Akt phosphorylation, and thereby orchestrate downstream signaling pathways that favor viral replication, survival, and immune evasion. Transient activation of this pathway supports viral replication, whereas sustained signaling promotes latent infection and oncogenesis, particularly in Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus. This review provides a comparative analysis of PI3K/Akt pathway manipulation across all HHVs, highlighting shared strategies and virus-specific adaptations. We further discuss ongoing clinical trials and therapeutic opportunities targeting the PI3K/Akt axis, emphasizing its potential as a host-directed antiviral and anticancer strategy. Full article