Search Results (298)

To evaluate the epidemiology of herpetic keratitis over a 15-year period at a tertiary care center in Switzerland, focusing on the relative incidence of herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV), gender distribution, and co-infections, we conducted a retrospective single-center analysis of polymerase chain reaction (PCR) assays from corneal and conjunctival scrapings of suspected herpetic keratitis at a tertiary referral hospital. Patient demographics, viral spectra, and microbiological co-infections were assessed. Between 2010 and 2025, we identified 9954 PCR assays from 2892 patients, with 482 samples testing positive for herpesvirus. HSV-1 was the most frequent pathogen (328 of 3358, 9.8%), followed by VZV (143 of 3112, 4.6%), HSV-2 (9 of 3290, 0.27%), and CMV (2 of 194, 1.0%). Triplet testing (simultaneous HSV-1, HSV-2, and VZV-PCR) enabled direct comparisons of relative incidence rates. We found 2913 triplet testing results, with a relative distribution in positive results of 65.4% for HSV-1, 32.5% for VZV, and 2.1% for HSV-2. HSV-1 keratitis had a statistically significant higher incidence in men (58.9%, p = 0.0044), while no sex difference was detected for VZV (47.9%, p = 0.6683), HSV-2 (33.3%, p = 0.5078), or CMV (100%, p = 0.500). Bilateral infections were present in two patients, and co-infections were detected as follows: 8 cases of HSV-1/VZV co-detection, 3 cases of Acanthamoeba, and 15 of fungi. HSV-1 was the overwhelmingly dominant cause of herpetic keratitis at our institution, occurring more than twice as frequently as VZV and vastly outnumbering HSV-2. The statistically significant higher incidence in men in HSV-1 keratitis suggests possible biological or sociodemographic influences, whereas co-infections highlight the complexity of corneal pathology in a referral setting. These findings underscore the importance of multiplex PCR testing for accurate pathogen detection and provide insights into the epidemiologic landscape of herpetic keratitis. Full article

Autoimmune flares are often accompanied by abrupt surges of circulating plasmablasts—short-lived, high-output antibody-secreting cells generated through extrafollicular B-cell activation in response to microbial cues. Three categories of microbial input appear to repeatedly trigger these “plasmablast storms”: latent herpesvirus reactivations (Epstein–Barr virus, cytomegalovirus, human herpesvirus-6, varicella–zoster virus), acute respiratory or gastrointestinal infections including SARS-CoV-2, and chronic oral or gut dysbiosis. Although biologically distinct, these stimuli converge on innate sensing pathways driven by pathogen-associated molecular patterns such as unmethylated CpG DNA, single-stranded RNA, lipopolysaccharide, and bacterial lipoglycans. Through Toll-like receptors and type I interferon signalling, microbial signatures accelerate class switching, amplify inflammatory cytokine milieus, and lower B-cell activation thresholds, enabling rapid plasmablast mobilisation. Dysbiosis further maintains B cells in a hyper-responsive state by disrupting mucosal homeostasis and altering microbial metabolite profiles, thereby reducing the stimulus required to trigger plasmablast bursts. Once generated, these waves of oligoclonal plasmablasts home to inflamed tissues, where chemokine and adhesion landscapes shape their retention during flares. Emerging evidence suggests that such episodic plasmablast expansions promote autoantibody diversification, somatic hypermutation, and epitope spreading, progressively eroding tolerance. This review synthesizes these insights into a unified model in which infections and dysbiosis promote microbe-licensed plasmablast storms that influence the tempo and severity of autoimmune disease. Full article

Background: Herpes zoster (HZ) represents a substantial public health concern among aging populations, yet regional variability in clinical patterns and risk determinants remains insufficiently documented. In southeastern Romania, epidemiological data are limited, and the combined influence of demographic, behavioral, and metabolic factors on disease severity has not been systematically evaluated. Methods: We performed a retrospective observational study including 100 consecutive patients diagnosed with HZ between 2019 and 2023 in a dermatology department in southeastern Romania. Demographic characteristics, lifestyle behaviors, anthropometric status, clinical manifestations, and outcomes were extracted from medical records. Associations between categorical variables were assessed using Chi-square tests and Cramer’s V, while interaction patterns were explored through log-linear modeling. Heatmaps were generated in Python (version 3.10) using the Matplotlib library (version 3.7.1) to visualize distribution patterns and subgroup relationships. Results: The cohort showed a marked age dependence, with 77% of cases occurring in individuals ≥ 60 years, consistent with immunosenescence-driven reactivation. Women represented 59% of cases, and 84.7% of female patients were postmenopausal. Urban residents predominated (91%). Vesicular eruption (84%) and acute pain (79%) were the most frequent symptoms. Localized HZ was observed in 81% of cases, while ophthalmic involvement (11%) and disseminated forms (8%) were less common. Lifestyle factors significantly influenced clinical severity: smokers, alcohol consumers, and sedentary individuals exhibited higher proportions of postherpetic neuralgia (PHN) and ocular complications (p < 0.001). Overweight and obese patients demonstrated a higher burden of PHN, suggesting a role for metabolic inflammation, although BMI was not associated with incidence. No significant association between age category and complication type was detected, likely due to small subgroup sizes despite a clear descriptive trend toward increased severity with advanced age. Conclusions: These findings support a multifactorial model of HZ severity in southeastern Romania, shaped by age, lifestyle behaviors, hormonal status, and metabolic risk. While incidence patterns align with international data, the strong impact of modifiable factors on complication rates highlights the need for targeted prevention and individualized risk assessment. Results offer a regional perspective that may inform future multicenter investigations. Full article

Background: Herpes zoster (HZ), caused by the reactivation of varicella-zoster virus (VZV), primarily affects elderly populations worldwide. Although current recombinant HZ vaccines show strong immunogenicity, their high cost and potential side effects may limit their widespread use. Therefore, developing a cost-effective HZ vaccine with improved safety profiles would have significant clinical and public health implications. Methods: Building upon our previously optimized truncated gE (tgE350) from VZV, we developed the tgE350 + Fe nanoparticle vaccine using SpyTag/SpyCatcher covalent conjugation. The tgE350 protein (with a SpyTag tag) and the Fe protein (with a SpyCatcher tag) were expressed in HEK293F and E. coli BL21, respectively, enabling spontaneous nanoparticle assembly. Protein expression and nanoparticle formation were confirmed through SDS-PAGE and negative-stain electron microscopy. BALB/c mice were inoculated with either tgE350 + Fe or tgE350 combined with Al and CpG adjuvants. Immune responses were evaluated using ELISpot and flow cytometry for cellular immunity, along with ELISA, VZV microneutralization, and fluorescent antibody membrane antigen (FAMA) assays for antibody titers. Histopathological examination of major organs ensured vaccine safety. Results: Compared with the truncated vaccine tgE350, the nanoparticle vaccine tgE350 + Fe significantly enhanced VZV neutralizing antibodies and specific antibody responses in mice without causing significant changes in lymphocyte populations (no difference from the control group). Moreover, the tgE350 + Fe group had significantly more lymphocytes secreting IFN-γ, IL-2, and IL-4 than the tgE350 group. No apparent pathological damage was observed in the heart, liver, spleen, or lungs of mice in any experimental group. Conclusions: This experiment successfully developed the HZ nanoparticle vaccine tgE350 + Fe. It enhanced VZV-specific neutralizing antibodies, generated better cellular and humoral immune responses, and demonstrated good safety. Full article

Background/Objectives: Polymerase chain reaction (PCR) testing of ocular fluids is an essential diagnostic method for identifying infectious causes of uveitis. However, multiplex PCR kits specifically developed for ophthalmic use are not commercially available in many regions, including Korea. Given the biochemical similarity between cerebrospinal fluid (CSF) and aqueous humor, this study evaluated the diagnostic utility of a commercially available CSF multiplex PCR panel for detecting herpesviruses in patients with suspected viral uveitis. Methods: We retrospectively reviewed the medical records of patients whose aqueous humor samples were analyzed using a multiplex PCR assay originally designed for CSF testing (Seeplex Meningitis-V1 ACE Detection kit, Seegene, Seoul, Republic of Korea). The samples were obtained between May 2019 and June 2023 at two tertiary referral hospitals. The assay targeted herpes simplex virus types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), cytomegalovirus (CMV), Epstein–Barr virus (EBV), and human herpesvirus 6 (HHV-6). Patients were classified into three groups: (I) anterior uveitis with suspected herpesviral infection, (II) acute retinal necrosis (ARN), and (III) CMV retinitis. Baseline characteristics, PCR positivity rates, and virus prevalence were compared among the groups. Results: Among 149 eyes tested, 86 were included in the final analysis. The overall positivity rate was 38.4%. PCR positivity was 19.7% (12/61) in Group I, 93.8% (15/16) in Group II, and 66.7% (6/9) in Group III. CMV was the most common pathogen in Groups I (66.7%) and III (100%), while VZV was predominant in Group II (80%). No HHV-6 infection was detected. Conclusions: The positivity rate in anterior uveitis (Group I) was lower than previously reported, likely due to the limited sample volume relative to the assay’s requirement. Nevertheless, the assay demonstrated diagnostic reliability comparable to previous reports for ARN and CMV retinitis. Therefore, the CSF-based multiplex PCR panel serves as a feasible and cost-effective diagnostic option for sight-threatening posterior segment infections, facilitating prompt diagnosis and treatment, although further optimization is warranted for anterior uveitis. Full article

Varicella-zoster virus (VZV) is a human neurotropic herpesvirus. The primary infection with VZV causes chickenpox and establishes latency in sensory and dorsal root ganglia. Viral reactivation leads to herpes zoster (HZ), which is accompanied by complications such as postherpetic neuralgia (PHN), causing a significant disease burden. At present, vaccination is the most effective preventive measure. We developed a recombinant zoster vaccine, gE/BFA01, which comprises truncated VZV glycoprotein E and the liposome-based adjuvant BFA01 (containing MPL and QS-21). In this study, we evaluated the recombinant zoster vaccine’s immunogenicity in a live attenuated VZV-primed C57BL/6N mouse model and explored the mechanism of action of the BFA01 adjuvant. The results indicate that the gE/BFA01 vaccine induces superior antibody responses and stronger cellular immune responses compared with gE with aluminum hydroxide. Furthermore, gE/BFA01 showed comparable immunogenicity to the licensed vaccine Shingrix. Mechanistic investigations revealed that the BFA01 adjuvant can enhance the recruitment of innate immune cells at the injection site, increase the expression of DCs surface maturation markers, and activate multiple inflammatory signaling pathways in lymph nodes. Collectively, these findings indicate that gE/BFA01 can induce potent humoral and cellular responses, supporting its further development as a high-efficiency vaccine candidate. Full article

Background: Universal varicella vaccination has fundamentally altered the epidemiology of varicella-zoster virus (VZV) infections. While the incidence of primary varicella has declined, the characteristics of herpes zoster (HZ) in the post-vaccine generation remain a subject of debate. This study aimed to analyze the demographic and clinical characteristics of pediatric HZ in the context of a mature national immunization program. Methods: This retrospective observational study included children under 18 years of age diagnosed with HZ between 2018 and 2025 at the dermatology outpatient clinic of a tertiary hospital. Demographic, clinical, and epidemiologic variables were retrieved from hospital records. Results: A total of 64 pediatric patients (mean age: 10.5 ± 4.9 years; 59.4% male) were analyzed. The majority (93.8%) were vaccinated. Vaccinated children presented at a significantly younger age (mean: 9.1 ± 5.4 years) than those with a history of natural varicella infection without vaccination (mean: 12.3 ± 3.5 years; p = 0.007). The thoracic (39.1%) and cervical (35.9%) dermatomes were most frequently affected. Cervical involvement was significantly more frequent in younger children (mean age 7.1 years), whereas thoracic and lumbar dermatomes predominated in adolescents (mean age > 12 years; p = 0.001). Seasonal distribution was even, but the annual frequency peaked in 2023, whereas 2021 showed the lowest number. Only one patient (1.6%) developed postherpetic neuralgia, and no other complications were observed. Conclusions: Universal vaccination is associated with a shift in the onset of pediatric herpes zoster to younger individuals, often presenting with cervical dermatomal involvement hypothesized to be linked to vaccination injection sites. Clinicians should recognize that while HZ in vaccinated children is typically a self-limiting event that does not require an extensive immunologic workup in otherwise healthy, immunocompetent children, rare complications like postherpetic neuralgia can still occur. Limitations of this sin-gle-center, retrospective study include a high exclusion rate due to missing data, a small number of unvaccinated comparators, and the lack of viral genotyping to differentiate wild-type from vaccine-strain virus. Full article

The epidemiology of central nervous system (CNS) infections caused by herpesviruses varies with host factors and geographic distribution. Timely diagnosis and therapeutic intervention are life-saving. This study investigated the epidemiology of herpesvirus CNS infections in Western Greece, compared clinical and laboratory findings with international data and evaluated an internal laboratory algorithm for cerebrospinal fluid (CSF) molecular testing criteria. During the study period, 940 of 4300 CSF samples met eligibility criteria for RT-PCR detection of herpes simplex virus (HSV-1, HSV-2) and varicella zoster virus (VZV). Of these, 53 (5.63%) were positive: 37 VZV, 9 HSV-1, and 7 HSV-2. HSV-2 cases occurred in younger patients (median age 41) and had the highest CSF white blood cells (WBC) counts (231/mm³), followed by VZV (125/mm³) and HSV-1 (26/mm³). CSF protein was higher in HSV-2 infections. Magnetic resonance imaging (MRI) was the most sensitive imaging modality for detecting CNS inflammation. These results indicate VZV as the predominant herpesvirus in this region, underscoring the need for high clinical suspicion in older patients and timely molecular diagnosis. Full article

The research of Prof. Dr. Thomas C. Merigan has spanned almost half a century. It started in 1963 with his interest in interferon (i). He then identified pyran copolymer as a synthetic polyanionic inducer of interferon (ii), and thereafter thiophosphate-substituted polyribonucleotides, i.e., poly r($\overline{\mathrm{s}}$A-$\overline{\mathrm{s}}$U) (iii). He recognized the potential of interferon as a therapeutic agent for virus infections (iv), varicella-zoster virus (VZV) being the first case in point (v). His interest then shifted to the treatment of herpes virus [herpes simplex virus (HSV) and cytomegalovirus (CMV)] infections (vi) and hepatitis B virus (HBV) infections (vii), to end up with human immunodeficiency virus (HIV) infections (viii, ix, x). T.C. Merigan’s pioneering work on the treatment of so many pivotal virus infections deserves further in-depth clinical evaluation. Full article

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem illness with unknown etiology. An estimated 17–24 million people representing approximately 1% of the population are afflicted worldwide. In over half of cases, ME/CFS onset is associated with acute “flu-like” symptoms, suggesting a role for viruses. However, no single virus has been identified as the only etiological agent. This may reflect the approach employed or more strongly the central dogma associated with herpesviruses replication, which states that a herpesvirus exists in two states, either lytic or latent. The purpose of this review is to address the role that abortive lytic replication may have in the pathogenesis of ME/CFS and other post-acute viral infections and also to raise awareness that these syndromes might be poly-herpesviruses mediated diseases. Full article

Varicella Zoster Virus (VZV), responsible for chickenpox and herpes zoster, has emerged as a significant contributor to cerebrovascular disease. Mounting evidence indicates that VZV reactivation may precipitate ischemic and hemorrhagic stroke through mechanisms of viral vasculopathy, immune evasion, and vascular inflammation. While antiviral therapy remains the cornerstone of treatment, several adjunctive regimens exhibit encouraging results in controlling endothelial inflammatory response. This targeted review synthesized findings from 31 studies, including clinical cohorts, in vitro models, and pathological analyses, to evaluate the relationship between VZV and stroke, with emphasis on treatment management beyond antivirals. Evidence demonstrates that VZV antigens are frequently detected within cerebral arteries, where they induce transmural inflammation, endothelial dysfunction, and thrombosis, thereby increasing stroke risk, particularly in the weeks following herpes zoster. Adjunctive therapies such as corticosteroids, statins, and resveratrol show promise in mitigating vascular inflammation, though clinical validation is limited. Preventive measures, especially zoster vaccination, significantly reduce herpes zoster incidence and may lower subsequent stroke risk, yet global uptake remains insufficient. Collectively, the data underscore the need for improved diagnostic tools, combination treatment strategies, and expanded vaccination programs to address the substantial public health burden of VZV-associated stroke. Full article

Background: Patients with autoimmune rheumatic diseases (ARDs) such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are at increased risk of infections due to immune dysregulation and immunosuppressive therapy. Vaccination is a cornerstone of infection prevention, but uptake is still inadequate. Methods: We conducted an observational, multicenter study at four Italian rheumatology centers. Adult patients with RA or SLE on immunosuppressive therapy completed a standardized questionnaire assessing demographics, disease activity, treatments, vaccination status for influenza, pneumococcus, varicella-zoster virus [VZV], hepatitis B virus [HBV], human papillomavirus [HPV], adverse events, and reasons for or against vaccination. Results: A total of 325 patients were included (226 RA, 99 SLE; median age 60 years; 84.6% females). Overall vaccine coverage was 68.0%, with influenza being the most frequent (54.2%), followed by pneumococcal (30.8%), HBV (21.2%), VZV (12.9%) and HPV (5.9%). RA patients showed higher influenza and pneumococcal uptake, while HBV vaccine was more common in SLE. Education was associated with higher pneumococcal and HBV coverage in both groups. Major adverse events and disease flares were rare. Physician recommendation was the main motivator, with rheumatologists driving VZV uptake and general practitioners influencing influenza and HBV. Among unvaccinated patients, the leading barrier was not being offered vaccination (42.5%), followed by concerns about efficacy/safety (18.3%) and lack of awareness (15.7%). Cluster analysis identified three subgroups: “Not offered” (largest), “Unaware,” and “Skeptical,” with age distribution differing across clusters. Conclusions: Vaccination coverage among Italian ARD patients remains insufficient. Physician recommendation is pivotal, while lack of physician offer and awareness are major barriers. Targeted educational strategies and proactive physician involvement are needed to improve vaccine uptake in this high-risk population. Full article

Background/Objectives: Varicella-zoster virus (VZV) causes herpes zoster (HZ/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8⁺ T-cell responses. Addressing this, we utilized the novel replication-defective chimpanzee adenovirus vector ChAdOx1 to construct the ChAdOx1-VZV (CVE) vaccine, using full-length glycoprotein E (gE) as antigen. This study evaluated the immunogenicity of a heterologous intramuscular (IM) prime/intranasal (IN) boost regimen with the aim of developing a novel VZV vaccine candidate. Methods: BALB/c mice were immunized with CVE using homologous or heterologous prime-boost regimens via IM or IN. And cynomolgus macaques were immunized intramuscularly with three doses of CVE. Cellular responses were assessed by intracellular cytokine staining (ICS) and IFN-γ ELISpot using splenocytes and PBMCs. Humoral responses were evaluated by serum gE-IgG ELISA and bone-marrow LLPC ELISpot. Memory subsets and tissue-resident T cells were analyzed by flow cytometry. Results: Heterologous IM prime/IN boost CVE regimen markedly enhanced both cellular and humoral responses, especially CD8⁺ T-cell responses. The induced LLPC and memory T cell responses indicate the potential for long-term protection against herpes zoster. In cynomolgus macaques, CVE induced robust serum gE-specific IgG responses and strong IFN-γ secreting T-cell activity, supporting the immunogenicity of CVE in a genetically distinct primate model and enhancing its clinical translational potential. Conclusions: CVE induces potent cellular and humoral immunogenicity, with IM prime/IN boost vaccination. Cross species immunogenicity observed in nonhuman primates further strengthens the translational relevance of this platform. These findings support CVE as a promising herpes zoster vaccine candidate and provide a rationale for continued evaluation in human-relevant systems. Full article

Background: Varicella zoster virus (VZV) remains a significant cause of pediatric morbidity in populations in Lebanon, yet comprehensive data on population immunity and vaccination uptake are limited. This study aimed to estimate VZV seroprevalence and identify factors associated with immunity and vaccine uptake among children and adolescents in Northern Lebanon. Methods: A cross-sectional study was conducted among 180 participants aged 1–18 years recruited from urban and rural settings in North Lebanon. After receiving informed parental consent, sociodemographic and clinical information were collected via structured questionnaires. Anti-VZV IgG and IgM antibodies were measured using validated Enzyme-Linked Immunosorbent Assays (ELISA). Associations with seropositivity and vaccination uptake were analyzed using multivariable logistic regression. Results: IgG seroprevalence was 79.4% (95% CI: 72.7–85.1), indicating prior exposure or immunization, while IgM antibodies, reflecting recent infection, were detected in 5.0% (95% CI: 2.3–9.4) of participants. Among vaccinated participants, IgG seropositivity was 63.6% (95% CI: 43.5–83.7) in the one-dose group and 89.5% (95% CI: 83.0–96.0) in the two-dose group. Completing the two-dose regimen was significantly associated with a higher IgG seropositivity (OR = 0.110, 95% CI: 3.2–52.4, p = 0.002). Parental reporting of history of varicella showed high sensitivity (99.0%) and overall accuracy (90.8%) in predicting seropositivity. Primary vaccination barriers included preference for natural infection (67%), perceived non-necessity (19%), and cost (10%). Regular pediatric follow-up strongly predicted vaccination (OR = 15.239, p < 0.001), whereas low parental awareness was associated with decreased vaccine uptake (OR = 0.027, p = 0.015). Conclusions: Suboptimal VZV vaccination coverage and persistent susceptibility underscore the need to integrate varicella vaccination into Lebanon’s national immunization schedule. Targeted educational efforts and enhanced pediatric healthcare engagement are critical to increasing vaccine uptake and reducing disease burden. Full article

The Varicella-zoster virus (VZV) open reading frame 54 (ORF54) gene encodes an 87 kDa monomer that oligomerizes to form the pORF54 portal dodecamer. Located at a single viral capsid vertex, the portal facilitates the translocation of the newly synthesized viral genome into the preformed empty capsid. Previously described α-methylbenzyl thiourea compounds were shown to inhibit VZV DNA encapsidation, likely by targeting pORF54. In this study, drug resistant isolates were obtained via passage of VZV in increasing concentrations of one analog, Compound I (Comp I). Mutations identified in four compound resistant isolates (amino acids 48, 304, 324 and 407) all localized to a region of the portal that was predicted to interface with capsid proteins. The portal is known to undergo significant conformational changes at the portal–capsid interface during DNA encapsidation. A set of recombinant viruses was designed to reveal the chemical and physical importance of each of the resistance mutations at the portal–capsid interface, the proposed binding site of the compound series. In addition, we employed a novel complementing cell line to show that despite the presence of the portal in the virion, DNA encapsidation did not occur. We propose that a-methylbenzyl thiourea compounds perturb interactions at or near the portal–capsid interface and prevent conformational changes needed to support DNA encapsidation. Full article