Herpesvirus Infection Research Articles

Infection-Associated Flares in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is characterised by generalised immune dysfunction, including infection susceptibility. Infection-associated flares (IAFs) are common and might rapidly self-resolve, paralleling infection resolution, but their specific clinical phenotype is poorly understood. Therefore, we screened 2039 consecutive visits and identified 134 flares, defined as a loss of the lupus low disease activity state (LLDAS), from 1089 visits at risk spanning over multiple follow-up years, yielding an average yearly LLDAS deterioration rate of 17%. Thirty-eight IAFs were isolated from the total flares and were mostly related to bacterial and herpesvirus infections. When compared to other flares (OFs; n = 98), IAFs showed no milder patterns of organ involvement and similar rates of long-term damage accrual, as estimated by conventional clinimetrics. Arthritis in IAFs was more severe than that in OFs [median (interquartile range) DAS-28 2.6 (2.3–4.1) vs. 2.0 (1.6–2.7); p = 0.02]. Viral IAFs were characterised by atypically lower levels of anti-DNA antibodies (p < 0.001) and possibly abnormally high complement levels when compared to flares of different origin. These data suggest that IAFs are of comparable or even higher severity than OFs and may subtend distinct pathophysiological mechanisms that are poorly tackled by current treatments. Further research is needed to confirm these data.

Computational design of prefusion-stabilized Herpesvirus gB trimers.

In the absence of effective vaccines, human-infecting members of the Herpesvirus family cause considerable morbidity and mortality worldwide. Herpesvirus infection relies on receptor engagement by a gH/gL glycoprotein complex which induces large-scale conformational changes of the gB glycoprotein to mediate fusion of the viral and host membranes and infection. The instability of all herpesvirus gBs have hindered biochemical and functional studies, thereby limiting our understanding of the infection mechanisms of these pathogens and preventing vaccine design. Here, we computationally stabilized and structurally characterized the Epstein-Barr virus prefusion gB ectodomain trimer, providing an atomic-level description of this key therapeutic target. We show that this stabilization strategy is broadly applicable to other herpesvirus gB trimers and identified conformational intermediates supporting a previously unanticipated mechanism of gB-mediated fusion. These findings provide a blueprint to develop vaccine candidates for these pathogens with major public health burden.

Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis

The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available. To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks. The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023. Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily. Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline. From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose. In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks. Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.

Herpesvirus surveillance in stranded striped dolphins (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus) from Italy with emphasis on neuropathological characterization.

Herpesvirus (HV) is widely distributed among cetacean populations, with the highest prevalence reported in the Mediterranean Sea. In this study, a comprehensive analysis was conducted, including epidemiological, phylogenetic, and pathological aspects, with particular emphasis on neuropathology, to better understand the impact of HV in these animals. Our results show a higher presence of HV in males compared to females, with males exhibiting a greater number of positive tissues. Additionally, adults were more frequently affected by HV infection than juveniles, with no infections detected in calves or neonates. The affected species were striped (Stenella coeruleoalba) and bottlenose dolphins (Tursiops truncatus). The highest positivity rates were observed in the genital system, cerebrum, and skin tissues. Phylogenetic analysis indicated a higher occurrence of Gammaherpesvirus (GHV) sequences but increased genetic diversity within Alphaherpesvirus (AHV). Key neuropathological features included astro-microgliosis (n = 4) and meningitis with minimal to mild perivascular cuffing (n = 2). The presence of concurrent infections with other pathogens, particularly cetacean morbillivirus (CeMV), underscores the complex nature of infectious diseases in cetaceans. However, the presence of lesions at the Central Nervous System (CNS) with molecular positivity for GHV, excluding the involvement of other potential neurotropic agents, would confirm the potential of this HV subfamily to induce neurological damage. Pathological examination identified lesions in other organs that could potentially be associated with HV, characterized by lymphoid depletion and tissue inflammation. These findings enhance our understanding of HV in odontocetes and highlight the need for ongoing research into the factors driving these infections and their broader implications.

Loopy virus or controlled contortionist? 3D regulation of HCMV gene expression by CTCF-driven chromatin interactions.

Three-dimensional chromatin control of eukaryotic transcription is pivotal for regulating gene expression. This additional layer of epigenetic regulation is also utilized by DNA viruses, including herpesviruses. Dynamic, spatial genomic organization often involves looping of chromatin anchored by host-encoded CCCTC-binding factor (CTCF) and other factors, which control crosstalk between promoters and enhancers. Herein, we review the contribution of CTCF-mediated looping in regulating transcription during herpesvirus infection, with a specific focus on the betaherpesvirus, human cytomegalovirus (HCMV).

Genome-wide CRISPR screens identify CLC-2 as a drug target for anti-herpesvirus therapy: tackling herpesvirus drug resistance.

The emergence of drug resistance to virus (i.e., acyclovir (ACV) to herpesviruses) has been termed one of the common clinical issues, emphasizing the discovery of new antiviral agents. To address it, a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screening was performed in mouse haploid embryonic stem cells infected with pseudorabies virus (PRV), an α-herpesvirus causing human and pig diseases. The results demonstrated that type 2 voltage-gated chloride channels (CLC-2) encoded by one of the identified genes, CLCN2, is a potential drug target for anti-herpesvirus therapy. CLC-2 inhibitors, omeprazole (OME) and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), can efficiently inhibit infection of multiple herpesviruses in cellulo (i.e., PRV, HSV and EBV), and effectively treat murine herpes simplex encephalitis (HSE). Additionally, DIDS was found to inhibit HSV-1 replication by blocking the PI3K/Akt pathway. Most importantly, both DIDS and OME were able to inhibit ACV-resistant HSV-1 strain infection. The study's findings suggest that targeting host-cell factors such as CLC-2 may be a promising approach to tackling herpesvirus drug resistance. The discovery of CLC-2 as a potential drug target for anti-herpesvirus therapy provides a new direction for the development of novel antiviral agents.

Herpesvirus Antibody Response and Occurrence of Symptoms in Acute and Post-Acute COVID-19 Disease.

Knowledge about the underlying causes of the individual occurrence of symptoms during acute COVID-19 disease and during the post-acute sequelae of COVID-19 is limited. In a German COVID-19 follow-up study, we assessed whether elevated antibody responses to herpesviruses were associated with symptom occurrence in acute COVID-19 disease (n = 96 participants) and during 20 months of follow-up (n = 62 participants). Serum samples were analyzed for their antibodies to herpes simplex virus (HSV)-1 and -2, Epstein-Barr virus (EBV), and Cytomegalovirus (CMV) using fluorescent bead-based multiplex serology. The association of herpesvirus antibodies with symptom occurrence (fatigue, fever, dyspnea, decrease in taste, concentration problems) was assessed using multivariate logistic regression models. High EBV antibody levels were significantly associated with a more than fourfold increased odds of experiencing fatigue during acute COVID-19 disease and during follow-up. High CMV antibody levels were significantly associated with a more than threefold increased odds of experiencing concentration problems and a decrease in taste during the follow-up. The HSV-1 and -2 antibody levels were not elevated in the individuals that experienced symptoms. In conclusion, our findings indicate that herpesvirus infections, specifically EBV and CMV infections, might play a role in symptom development during acute and post-acute COVID-19 disease. It remains to be elucidated whether the elevated EBV and CMV antibodies determined in our study are indicators of herpesvirus reactivation.

Infection risk with JAK inhibitors in dermatoses: a meta-analysis.

Evolving evidence suggests that Janus Kinase Inhibitors (JAKi) may predispose to certain infections, including tuberculosis and human herpes viruses. This review aimed to compare the infection risk in patients on a systemic JAKi for a dermatologic indication to a placebo. A systematic review was carried out from inception to June 2023, using the EMBASE, Medline, SCOPUS, and Cochrane Library of Registered Trials databases. Eligible studies included placebo-controlled randomized trials that investigated the incidence of infection in patients with a dermatologic indication. Primary outcomes included the most commonly reported infections pertaining to serious and opportunistic infections, upper respiratory tract infections, nasopharyngitis, herpes simplex, varicella zoster, tuberculosis, neutropenia, and lymphopenia. A meta-analysis of incidence ratios was conducted to determine odds ratios (OR), with a 95% confidence interval (CI) analysis. The meta-analysis found no increased risk of serious (OR: 0.92, 95% CI: 0.61-1.43, P = 0.74) or opportunistic infections (OR: 0.65, 95% CI: 0.32-1.31, P = 0.23). The incidence of varicella-zoster infections was significantly higher in the JAKi cohort (OR: 1.72, 95% CI: 1.08-2.72, P = 0.022). From 25 studies, there was no overall increased risk of herpes simplex infections (OR: 1.43, 95% CI: 0.93-2.23, P = 0.102) to placebo; however, a significantly higher risk in those with atopic dermatitis to alopecia areata was demonstrated (OR: 1.73, 95% CI: 1.13-2.69, P = 0.013). The results of this analysis do not suggest an increased risk of serious and opportunistic infections in those on JAKi compared to placebo. However, they support an increased risk of varicella-zoster infections and a higher risk of herpes simplex infections in those with atopic dermatitis to alopecia areata. The results of this report support these agents' short-term safety but signal that vigilance should be practiced in patients at risk for serious or recurrent herpes virus infections.

Epidemiological characteristics of three herpesviruses infections in children in Nanjing, China, from 2018 to 2023.

To evaluate the epidemiology characteristics of Herpes simplex virus type 2 (HSV-2), Epstein-Barr virus (EBV) and Cytomegalovirus (CMV) infection in children from January 2018 to December 2023, in Nanjing, China. We conducted a retrospective analysis of 21,210, 49,494 and 32,457 outpatients and inpatients aged 1 day to 17 years who were subjected to the three herpesviruses (HSV-2, EBV, and CMV) nucleic acid testing from January 2018 to December 2023, respectively. Demographic information, laboratory findings, etc. were collected and analyzed. HSV-2, EBV and CMV nucleic acid testing were performed by real-time PCR. The total rate of detection of the three herpesviruses for all specimens was 0.32% (67/21,210), 14.99% (7419/49,494), and 8.88% (2881/32,457), respectively. A declining trend in the incidence of viral infections over the years was observed for the three herpesviruses (all P<0.05). The detection rate for HSV-2, EBV, and CMV was highest among patients aged 1-3 years, 3-7 years, and 28 days to 1 year, respectively (all P<0.05). The presence of HSV-2 and CMV infection did not exhibit a discernible seasonal pattern, whereas EBV typically demonstrated an elevation during the summer and autumn. EBV and CMV were both prevalent among children in China, except for HSV-2. The annual prevalence of the three herpesviruses show decreasing trend from 2018 to 2023, and no difference in gender (except for EBV). EBV infections usually occur in the summer and autumn, whereas HSV-2 and CMV do not exhibit significant seasonality. The positivity rate of HSV-2 is highest in 1-3 years, EBV is highest in 3-7 years, and that of CMV is highest in 28 days to 1 year. Positive detection rates are higher in outpatients than in inpatients.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Indirect Immunofluorescence Test for Detecting HSV-1, 2 in Patients with Esophageal Cancer: A Pilot Cross-Sectional Survey in Kazakhstan.

To evaluate the detectability of herpes simplex virus type 1 and 2 (HSV-1, 2) antigens in the esophageal mucosa in esophageal cancer. A cross-sectional pilot study with a control group was conducted from December 2022 to May 2023. The patients were divided into two groups: the main group with verified esophageal cancer and the control group without esophageal cancer based on the histological report. Diagnosis using fibroesophagogastroscopy (FEGS), histological analysis, and indirect immunofluorescence reaction (iIFR) was accomplished according to indications at the outpatient center of the endoscopic department of the Multidisciplinary Medical Center, Astana. Descriptive statistics and nonparametric methods were used to analyze the data. A total of 30 patients were recruited in the study, with 15 patients in the main group and 15 patients in the control group. HSV-1 and HSV-2 antigens were detected in the 13 cases (86.7%) during the study of biomaterial from patients with confirmed esophageal cancer in the main group and only in one case (6.8%) in the control group (95% CI 7.35 - 1126.9%, p=0.001). The presence of lymphocytic infiltration was detected in 13 cases (86.7%) in the main group and in 5 cases (33.3%) in the control group (95% CI 2.07 - 81.48%, p = 0.008). The process of keratinization was identified in HSV-1,2 antigens positive cases in the main group in 5 cases (35.7%) G1, in 5 cases (35.7%) G2, and in 3 cases (21.4 %) G3 (95% CI 1.66 - 656.23%, p=0.002). Overall, the local activity of herpesvirus infection to a certain extent influences the malignant potential of tumor cells and the resistance of surrounding healthy tissues. A large-scale study is still needed to confirm these results. The present pilot study provided an overview of a possible method for detecting HSV-1,2 activity in malignant tissue from esophageal cancer.

Kaposi's sarcoma-associated herpesvirus infection and its association with all-cause and cardiovascular mortality in the general adults: A prospective cohort study.

To investigate the association between Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV8) infection and both all-cause and cardiovascular mortality in a representative cohort of US adults, data from the National Health and Nutrition Examination Survey III (NHANES III; 1988‒1994) were analyzed, including 13,993 participants aged 18‒90 years who underwent KSHV serology evaluations. Mortality outcomes were ascertained through December 2019 using the National Death Index. Cox proportional hazards models were employed to examine the association between KSHV seropositivity and mortality, adjusting for potential confounders such as age, sex, ethnicity, body mass index, and serum TG. Over a median follow-up period of 26.5 years, 5503 deaths were recorded. KSHV seropositivity was associated with an increased hazard of all-cause mortality (Hazard Ratio [HR]: 1.32, 95% Confidence Interval [CI]: 1.03‒1.69) and cardiovascular mortality (HR: 1.58, 95% CI: 1.00‒2.50) after adjusting for age, sex, ethnicity, and body mass index. Notably, the association between KSHV infection and all-cause mortality persisted among women (HR: 1.32, 95% CI: 1.02‒1.72) after adjusting for all confounders, whereas the association with cardiovascular mortality was only statistically significant for men (HR: 1.90, 95% CI: 1.02, 3.53).KSHV infection may represent an independent risk factor for all-cause and cardiovascular mortality among US adults. These findings highlight the need for further research to validate these associations in independent populations and to elucidate the biological mechanisms underlying the observed increased mortality associated with KSHV infection.

Unveiling the causal link between herpes virus infection and cutaneous leukocytoclastic angiitis: Insights from Mendelian randomization analysis

AbstractBackgroundCutaneous leukocytoclastic angiitis (CLA) is a clinically relevant condition, with previous studies suggesting an association with herpes virus infections. However, the causality of this association remains unclear. This study aimed to investigate the causal relationship between herpes viruses and CLA.MethodsGenetic variants linked to the herpes virus were retrieved from the Integrative Epidemiology Unit at the University of Bristol open genome‐wide association studies project and FinnGen database. Data on CLA, involving 262 CLA cases and 207,482 healthy controls, were obtained from the FinnGen consortium R7. Mendelian randomization (MR) analysis, including the inverse variance weighted (IVW), MR‐Egger, and weighted median methods, was performed. Sensitivity analyzes were conducted to ensure the accuracy of the results.ResultsOf the 15 herpes viruses investigated, only human herpesvirus 6 (HHV‐6) demonstrated a causal association with CLA (odds ratio: 1.886, 95% confidence interval: 1.053–3.378, p = 0.033), indicating that HHV‐6 infection significantly increases the risk of CLA. Furthermore, IVW and MR‐Egger tests for heterogeneity confirmed homogeneous MR analysis results without evidence of horizontal pleiotropy (p &gt; 0.05). No significant causal relationship was observed for other herpes viruses, such as herpes simplex virus, varicella‐zoster virus, cytomegalovirus, and Epstein‐Barr virus.ConclusionOur MR analyzes strongly support a causal relationship between HHV‐6 and CLA, elucidating the etiology of this condition and highlighting the potential of HHV‐6‐targeted therapeutic interventions in CLA treatment. However, further research is necessary to expound the underlying mechanisms and explore potential therapeutic interventions targeting HHV‐6‐associated CLA.

Changes in the cytotoxic and regulatory functions of NK cells in patients with long-COVID under the influence of the human herpesvirus 6 (pilot study).

Long-COVID are often accompanied by the development of autoimmun disorders. Such dysregulation of the immune system can be caused by reactivation of "sluggish" herpesvirus infection in patients after COVID-19. The one of the possible causes of autoimmunization is a change in the cytotoxic functions of NK cells under the influence of HHV6. The aim of research was to study the expression of receptor-ligand Fas-FasL, regulating marker CD38 and inhibitory receptor TIM-3 on NK cells in patients with long-COVID after mild, moderate, and severe stage of COVID-19 in the anamnesis with or without reactivation of HHV-6 and to identify risk factors for the formation of autoimmune disorders in these patients. This study investigated 124 adults (73 female and 51 male) aged 18 to 65years with long-COVID. The groups of patients with long-COVID were divided depending on mild, moderate, and severe forms of COVID-19 in the anamnesis and with/without reactivation of HHV-6. The control group included 20 healthy participants. Molecular genetic studies (PCR) were performed for all patients to detect the existence of DNA HHV6. Multiparametric flow cytometry was performed on 124 EDTA peripheral blood samples collected from long-COVID patients and 20 healthy controls. There was defined an imbalance between acute antiviral mechanisms, the response contributing to tissue damage and immunopathology, probably autoimmunity in patients with long-COVID after different forms of COVID-19 with reactivation of HHV-6. The presence of HHV-6 in groups with long-COVID was accompanied by higher expression of FasL and CD38, especially in patients, who had a severe form of COVID-19 in the anamnesis. The decrease in TIM-3 in patients with reactivation of HHV-6 compared to patients without HHV-6 puts the preservation of immunological tolerance at risk of Th1-dependent immune responses. The reactivation of HHV-6 is accompanied by higher expression of FasL and CD38, which indicates increased hyperactivation of NK cells, their cytotoxic activity, and subsequent exhaustion. NK cells of these patients lose their immunoregulatory ability, this creates prerequisites for the development of immunopathology, probably autoimmune processes.

Clinical and immunological characteristics of post-covid patients with infectious immunopathology syndrome

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has caused global morbidity and high mortality worldwide. Today it is known that, despite recovery from COVID-19, confirmed by both laboratory and instrumental diagnostic methods, many patients, regardless of the severity of the disease, suffer from a significant deterioration in health and increased exacerbations of chronic diseases. During examinations by attending physicians, they note fatigue, an increase in cases of acute respiratory viral infections per year, an increase in relapses of skin diseases such as furunculosis, pyoderma, exacerbation of pulmonary pathologies, pathologies of the urinary tract of inflammatory origin, as well as chronic infectious diseases such as herpesvirus and human papillomavirus infections, which occur for the first time or are characterized by frequent relapses no less than six months after recovery from acute COVID-19. Such persistent post-infectious consequences are known as post-COVID syndrome. SARS-CoV-2 infection is accompanied by damage to both the acquired and innate immune systems. In previous work, we determined the role of B cells, cytotoxic T lymphocytes, natural killer cells and the regulatory properties of CD46, as well as its involvement in the processes of viral entry into the cell. In this study, we studied the relationship of immune disorders of these factors of innate and acquired immunity with the clinical manifestations of post-COVID infectious syndrome in this category of patients and the severity of lung damage in these patients during the acute period of COVID-19. The results of the study showed that in some patients more than six months after suffering from COVID-19, the following was revealed: in patients who had a coronavirus infection without lung damage, no violations of the innate and acquired parts of the immune system were detected. In addition, significant differences were identified between clinical manifestations of diseases with increasing cases of relapses or newly identified after clinical recovery from an acute COVID-19 infection, depending on the phenotype of immune status disorders.

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Formulation and Evaluation of Famciclovir Microsphere Loaded Capsule for the Treatment of Herpes Virus Infection

Viral Infection and Ischemic Stroke: Emerging Trends and Mechanistic Insights.

Population studies have suggested that viral infections may be contributing to risk of ischemic stroke, although the mechanisms for this are unclear. In this review, we examine the epidemiological evidence supporting the involvement of viral diseases, including influenza, COVID-19, chronic herpesvirus infections, and hepatitis C in current trends of stroke incidence. To support these associations, we highlight the virus-host interactions that are critical in the context of stroke, including direct effects of acute and persistent viral infections on vascular function, inflammation, and thrombosis. Additionally, we evaluate the systemic changes that occur during viral infection that can predispose individuals to ischemic stroke, including alterations in blood pressure regulation, coagulation, and lipid metabolism. Our review emphasizes the need to further elucidate precise mechanisms involved in viral infections and stroke risk. Future research will inform the development of targeted interventions for stroke prevention in the context of viral diseases.

Fatal infection caused by a genetically distinct elephant endotheliotropic herpesvirus type 5 in a captive Asian elephant in Germany

BackgroundElephant endotheliotropic herpesvirus (EEHV) infection is the most common cause for lethal hemorrhagic disease in captive juvenile Asian elephants (Elephas maximus). Although EEHV1 is known as the most likely cause of fatal haemorrhagic disease in Asian elephants, EEHV5 was lately involved in lethal cases of haemorrhagic disease in captive elephants.Case presentationHere we report the first death of a four-year old Asian elephant diagnosed with EEHV5 in Germany. Molecular diagnosis yielded detection of EEHV5 DNA in all tested tissues. Histopathological examination revealed typical features of hemorrhagic disease in all examined organs. EEHV5 was sequenced from total DNA isolated from heart tissue by Illumina and Nanopore sequencing. Sequencing data showed 3,881 variants, distributed across the entire genome, compared to the published EEHV5 sequence.ConclusionsWe have detected EEHV5 in a fatal disease case of a male Asian elephant. Whole genome sequencing revealed substantial differences of our DNA isolate compared to available EEHV5 sequences. This report of fatal haemorrhagic disease associated with EEHV5 infection should raise awareness for EEHV5 as an important elephant pathogen. Genome sequencing and downstream SNPs analysis will further encourage future research to understand genetic diversity, pathogenesis and virulence of EEHVs with respect to developing new diagnostic methods, prophylactic strategies, and implementation of surveillance and control measures.

Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity.

Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.

Propagation of koi herpesvirus using embryonated chicken eggs: a potential substitute method for fish vaccine production?

Koi herpesvirus disease (KHVD) is caused by a large DNA virus that commonly infects carp, Cyprinus carpio (koi and common carp). KHVD has spread rapidly across the globe and caused high mortality in all ages of common carp and koi. Until now, no effective treatment has been applied to prevent KHV infection impacting the mass production of koi and common carp . An environmentally friendly alternative strategy for controlling fish disease is vaccination. One of the challenges facing conventional viral vaccine production is the requirement for koi or common carp cell cultures, which must be frequently maintained with expensive materials required for virus propagation. This study aims to obtain KHV that has been propagated in embryonated chicken eggs (ECE) to formulate an affordable KHV vaccine for the aquaculture industry. This research consisted of three stages; the first stage was virus inoculation into various parts of eggs (allantoic fluid, chorioallantoic membrane, amniotic fluid, and egg yolk). The second stage was observing viral growth and collecting ECE fluid and membranes. The third stage involved quantitatively determining the viral genomic copy numbers using the quantitative Polymerase Chain Reaction (qPCR) assay. KHV propagation in various parts of ECE resulted in varying viral genomic copy numbers with a high DNA copy number reported in allantoic fluid on the third day after inoculation. Further work is required to monitor virus titer in later passages and optimize methodology for using ECE as the potential alternative to cultured cells as the medium for virus propagation. In the future the system could be developed to produce promising vaccine candidates with more affordable vaccine prices for the Indonesian fish farming industry.