Search Results (128)

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

Background: There is growing evidence that uterine microbiota might be linked to endometrial receptivity (ER) and affect the outcome of assisted reproductive technology (ART) procedures. Owing to the invasive nature of endometrial sampling, the evaluation of microbiota in this biomaterial is only possible outside the embryo transfer (ET) cycle. However, menstrual blood might be the key to overcoming this challenge as it can be safely aspirated from the uterine cavity at the beginning of the target ET cycle. This study aimed to evaluate the association of the microbiological profiles of menstrual blood with ER in patients undergoing frozen ET. Methods: Menstrual blood was obtained from 98 individuals scheduled for frozen ET in a private ART clinic (ET success rate–50%). DNA was isolated from menstrual sediment and analyzed using a multiplex quantitative PCR assay designed to identify 28 relevant microbial taxa and 3 Herpesviridae viruses. Results: Bacterial DNA was detected in 75.5% of samples. There were no associations between the abundance of individual microbial taxa and the outcome of ET, and the same was true for Shannon’s α-diversity indices (p > 0.05). However, Candida spp. and Enterobacteriaceae were detected exclusively in patients with negative ET outcomes (p = 0.028). Individuals with recurrent implantation failure had a significantly lower abundance of Lactobacillus spp. than the rest (0.0 [0.0; 7.4] vs. 2.8 [0.0; 91.9] %, p = 0.024). Conclusions: Menstrual blood aspirated directly from the uterus is a promising biomaterial for endometrial microbiological profiling. Upon further investigation, its analysis might become a useful tool in managing infertile patients scheduled for ART treatment. Full article

Epstein–Barr virus is a globally disseminated oncovirus capable of causing various malignancies, including gastric cancer, Burkitt lymphoma, and Hodgkin’s lymphoma. The influence of recombination on the EBV genome revealed limitations in the current traditional EBV classification, and the extent of these recombination events across the EBV genome is not fully understood. The nuclear antigen 3C (EBNA3C) is an indispensable gene in the oncogenesis of the virus. Despite its critical role, little is known about EBNA3C sequence variability. We examined 988 EBNA3C gene sequences extracted from EBV genomes in this context. Among the protein motifs, the interaction sites with Nm23-H1, RBP-Jk, and nuclear localization signal (NLS) 2 and 3 were the most divergent between EBV types, while NLS-1 and the leucine zipper-like showed high conservation. In our study of the impact of recombination vs. point mutations in the EBNA3C gene, we found that recombination contributed five times more to substitutions than mutation. Notably, Asian populations exhibited the highest variability and recombination rates. Importantly, our analysis revealed geographical rather than disease-specific markers. Furthermore, filtering for recombination regions did not affect the classical classification of EBV-1 and EBV-2. This finding suggests that recombination is pivotal in the architecture of EBV genetic diversity of the EBNA3C gene. 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

Feline herpesvirus-1 (FHV-1) is taxonomically classified within the family Herpesviridae, subfamily Alphaherpesvirinae, genus Varicellovirus, and species Felid alphaherpesvirus 1. The genome of FHV-1 is 135,797 bp in length and encodes 74 proteins. Among these proteins, serine/threonine protein kinase (pK) and thymidine kinase (TK) have been identified as potential virulence factors in alphaherpesviruses, although these kinases are dispensable for viral replication. As kinases, regulating phosphorylation modification is one of their functions, while the mechanism by which phosphorylation modification affects cell physiological functions and thereby influences viral replication remains unclear. In this study, we generated pK- and TK-deficient FHV-1 mutants by CRISPR/Cas9-mediated homologous recombination. The pK-deficient virus produced significantly smaller plaques than the TK-deficient virus. The replication kinetics of the pK-deficient virus were attenuated in multistep growth compared to the TK-deficient virus. These results indicate that deletion of the pK gene markedly reduces the replicative capacity of FHV-1. We applied data-independent acquisition (DIA) quantitative proteomics to profile changes in global protein expression and phosphorylation in F81 cells upon infection with TK⁻, pK^−, and wild-type FHV-1 strain. The pK-deficient virus exhibited 3632 differentially phosphorylated proteins containing 11,936 modification sites; the TK-deficient virus showed 4529 differentially phosphorylated proteins with 19,225 phosphorylation sites. Functional characterization through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses identified significant involvement of phosphoproteins in spliceosome pathways in pK-deficient virus and ATP-dependent chromatin remodeling pathway in TK-deficient virus. Notably, several splicing regulators—including Ess-2 and CDK13, which modulate host spliceosomal function—displayed significantly reduced phosphorylation levels in pK-deficient viruses. A significant enrichment of ATP-dependent factors, such as SMARCA5 and RSF1, was observed in the TK-deficient virus. To our knowledge, this is the first investigation into the effects of FHV-1 infection on the host cell phosphoproteome. These data offer new insights into the phosphoregulatory circuits and signaling networks triggered by FHV-1 and may enhance our understanding of the FHV-1 replication mechanism. Full article

This study investigates the production of volatile organic compounds (VOCs) in RK-13 cells infected with three equine viruses representing different families: equine arteritis virus (EAV) (Arteriviridae), equine herpesvirus 1 (EHV-1) (Herpesviridae), and equine rhinitis B virus (ERBV) (Picornaviridae). VOCs, which are byproducts of cellular metabolism and potential non-invasive diagnostic markers, were analyzed using headspace solid-phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC-MS). Since viruses do not possess intrinsic metabolic activity, the observed changes in the VOC profiles were attributed to host responses, such as metabolic reprogramming, oxidative stress, and apoptosis. We hypothesized that each viral infection induces distinct metabolic changes, resulting in characteristic VOC signatures that mirror the virus type, replication kinetics, and cytopathic effects. Notably, viruses with rapid cytopathic effects (e.g., EHV-1) were anticipated to trigger more pronounced VOC alterations. In our experimental design, RK-13 cells were infected at a multiplicity of infection of 1 and incubated for 24 h, 48 h, or 72 h. Distinct VOC profiles emerged, with significant elevations in compounds like 2-ethyl-1-hexanol, particularly in EHV-1 infections, and selective increases in acetophenone and benzaldehyde. Principal component analysis (PCA) of the VOC concentration data showed the clear separation of data from viruses from different families. These findings support the potential of VOC profiling as a rapid diagnostic tool for viral infections. Full article

The Guinea Pig X Virus (GPXV), a newly identified gammaherpesvirus, provides an opportunity to study viral evolution and host–virus dynamics. This study characterizes the GPXV genome and investigates its phylogenetic relationships and divergence from related viruses through comparative genomic and phylogenetic analyses. Virus propagation was conducted in Vero cells, followed by genomic DNA extraction and pan-herpesvirus nested PCR. Sanger sequencing filled gaps in the initial genome assembly, and whole-genome sequencing was performed using the Illumina MiSeq platform. Phylogenetic analyses focused on ORF8 (glycoprotein B), ORF9 (DNA polymerase catalytic subunit), ORF50 (RTA: replication and transcription activator), and ORF73 (LANA: latency-associated nuclear antigen). Results showed that GPXV ORFs showed variable evolutionary relationships with other gammaherpesviruses, including divergence from primate-associated viruses and clustering with bovine and rodent viruses. In addition to phylogenetics, a comprehensive comparative analysis of protein-coding genes between GPXV and the previously described Guinea Pig Herpes-Like Virus (GPHLV) revealed divergence. Twenty-four non-ORF genomic features were unique to GPXV, while 62 shared ORFs exhibited low to high sequence divergence. These findings highlight GPXV’s distinct evolutionary trajectory and its potential role as a model for studying host-specific adaptations and gammaherpesvirus diversity. Full article

Periodontal diseases in pediatric subjects represent a challenging and relatively underexplored area compared to the extensive data available about periodontal diseases in adults. The present narrative review aims to explore the periodontal status and the related subgingival and/or salivary microbial profiles in pediatric subjects (≤18 years), focusing also on the state of health or systemic diseases. In healthy periodontium, early colonizers, such as Streptococcus and Actinomyces spp., dominate the subgingival microbiota, supporting an eubiosis state. Low levels of Candida albicans and latent Herpesviridae may be detected. In gingivitis, the microbial profile shifts towards more pathogenic species, including Prevotella intermedia and Fusobacterium nucleatum. In necrotizing gingivitis, typically affecting systemically compromised children, the microbial profile is characterized by spirochetes, Fusobacterium, and Prevotella intermedia. Viral coinfections—especially with HSV, CMV, and EBV—are more frequently detected. In periodontitis, the microbiota was dominated by red complex pathogens along with Aggregatibacter actinomycetemcomitans in the aggressive forms, especially in systemically compromised children, as Herpesviridae reactivation and co-infections. Fungal involvement is less well characterized; Candida albicans may be present, particularly in cases of severe immune suppression. Nevertheless, the lack of pediatric longitudinal studies investigating periodontal disease progression after periodontal treatment and related changes in microbiological composition limited the understanding and exploration of the oral microbiota over time. Full article

Herpes simplex virus (HSV) is a prevalent and persistent human pathogen belonging to the family Herpesviridae and classified as an alpha-herpesvirus. It comprises two distinct types, HSV-1 and HSV-2, which together infect a significant portion of the global population and pose substantial public health challenges. HSV-1 is typically associated with oral herpes, while HSV-2 primarily causes genital herpes; both are characterized by recurrent lesions, latent infection, and mucocutaneous discomfort. Conventional antiviral drugs such as acyclovir and its derivatives are limited by drug resistance, potential toxicity, and their inability to eradicate latent viral reservoirs. These limitations have prompted increasing interest in alternative therapeutic strategies. Phenolic acids and tannins, plant-derived polyphenolic compounds, have attracted considerable attention due to their potent antiviral properties against various viruses, including HSV. This review summarizes current research on phenolic acids and tannins as promising natural antivirals against HSV, with a focus on their mechanisms of action and efficacy in disrupting multiple stages of the HSV life cycle. Full article

Human activities and land use changes have a major impact on the distribution and diversity of mosquito vectors and their associated viruses. This study describes the diversity and differential abundance of viruses associated with mosquito species from four habitats of the Yucatan Peninsula, Mexico. Using next-generation sequencing (NGS), we analyzed 61 genomic libraries belonging to 20 mosquito species to characterize the viral community. A total of 16 viral species were identified, representing 14 different viral families. Most identified viruses were associated with insects, plants, and fungi. Additionally, vertebrate associated viral families, including Herpesviridae, Peribunyaviridae, Nairoviridae, and Arenaviridae, were detected in mosquitoes from urban habitats. Notably, insect-associated viruses like Hubei mosquito virus 4 and Hubei virga-like virus 2 were identified, along with the first report of Mercadeo virus in Mexico. Variations in viral community composition were primarily driven by mosquito species, with species of the same genus maintaining similar viromes despite occupying different habitats. These findings reinforce that intrinsic traits of mosquito species play a key role in shaping viral community composition. To our knowledge, this is the first study that describes the viral community in mosquitoes in Yucatan Peninsula, Mexico. This study provides essential baseline data for the surveillance of mosquitoes and associated viruses from a biodiverse tropical region that faces strong land use modifications. Full article

Duck plague (DP), caused by duck plague virus (DPV), is a highly contagious and fatal disease among waterfowl. UL3.5, an unconserved gene belonging to the Herpesviridae family, Alphaherpesvirinae subfamily, and Mardivirus genus, is located downstream of UL3 and exhibits high variability in size and sequence, with an absence in herpes simplex virus (HSV). Currently, there is little understanding of DPV UL3.5. In this study, we determined that DPV pUL3.5 is distributed within the cytoplasm and co-located with multiple organelles. In addition, we investigated the genetic type of DPV UL3.5 and found that it is an early gene encoding an early viral protein. To further explore the function of DPV UL3.5, we constructed DPV-BAC-δUL3.5 and discovered that the deletion of UL3.5 significantly impacts the viral secondary envelopment and release processes. Furthermore, the UL3.5-deleted virus shows defects in cell-to-cell spread. In conclusion, our findings demonstrate, for the first time, that the early viral protein encoded by DPV UL3.5 plays a crucial role in promoting viral replication. This offers fundamental insights for further investigations into the function of DPV UL3.5. Full article

We aim to investigate the role of the Herpesviridae family (HHV) in the onset and progression of prostate cancer (PCa) and to profile the local PCa immunological status. A total of 116 “tru-cut” biopsies (58 PCa and 58 benign prostatic hyperplasia [BPH]) and 49 formalin-fixed paraffin-embedded (FFPE) instances of PCa were analysed using real-time qPCR and histological examination. Infection with CMV, EBV, HHV6, and HHV7 was detected in 11.5% of the “tru-cut” biopsies (25.9% in BPH and 6.9% in the PCa group). In the formalin-fixed paraffin-embedded (FFPE) samples, infection was detected in 69.4% of the patients, with individual rates of EBV (47%), HHV6 (38%), HHV7 (41%), CMV (2.9%), HSV2 (2.9%), and VZV (5.8%). In the HHV-infected PCa cases, the histopathological landscape included intratumor lymphocyte infiltration with fibrosis and necrosis, periductal chronic inflammatory reaction and granulomatous lesions with foci of abscesses and necrosis, as well as inflammatory infiltration, chronic lymphadenitis, prostatic intraepithelial atrophy (PIA), and high-grade prostatic intraepithelial neoplasia (HGPIN). The majority of HHV-infected PCa patients were predominantly classified as grade G3/G4/G5 tumours, exhibiting perineural, perivascular, and lymphovascular invasion, seminal vesicle invasion, senile vesicle amyloidosis, and lymph node metastasis. Statistical analysis demonstrated a significant association between HHV infection and PCa (χ² ≈ 20.3, df = 1, p < 0.0001; Fisher’s exact test, p < 0.0001) with an odds ratio of 6.50 (95% CI: 2.80–15.12). These findings suggest that long-term HHV infection could contribute to a complicated and potentially altered immune PCa tumour environment due to inflammation. This may serve as a predictor of aggressive disease progression. Full article