Herpesvirus Infection Research Articles

Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking.

Rheumatoid arthritis (RA) is a chronic inflammatory and disabling disease that imposes significant economic and social costs. Tripterygium wilfordii Hook F (TwHF) has a long history of use in traditional Chinese medicine for treating joint disorders, and it has been shown to be cost-effective in treating RA, but its exact mechanism is unknown. The goal of the network pharmacology analysis and molecular docking was to investigate the potential active compounds and associated anti-RA mechanisms of TwHF. TCMSP and UniProt databases were searched for active compounds and related targets of TwHF. PharmGKB, DrugBank, OMIM, TTD, and the Human Gene Databases were used to identify RA-related targets. The intersected RA and TwHF targets were entered into the STRING database to create a protein-protein interaction network. R software was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking technology was used to analyze the optimal effective components from TwHF for docking with the selected target gene. Following screening and duplicate removal, a total of 51 active compounds and 96 potential targets were chosen. The PPI network revealed that the target proteins are CXCL8, CXCL6, STAT3, STAT1, JUN, PPARG, TP53, IL14, MMP9, VEGFA, RELA, CASP3, PTGS2, IFNG, AKT1, FOS, ICAM1, and MAPK14. The results of the GO enrichment analysis focused primarily on the response to lipopolysaccharide, the response to molecules of bacterial origin, and the response to drugs. The KEGG results indicated that the mechanisms were closely related to lipid and atherosclerosis, chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated, herpesvirus infection, hepatitis B, fluid shear stress and atherosclerosis, IL-17 signaling pathways, Th17-cell differentiation, and so on, all of which are involved in angiogenesis, immune cell chemotaxis, and inflammatory responses. Molecular docking results suggested that triptolide was the appropriate PTGS1, PTGS2, and TNF inhibitors. Our findings provide an essential role and basis for further immune inflammatory studies into the molecular mechanisms of TwHF and PTGS1, PTGS2, and TNF inhibitor development in RA.

Closing the Diagnostic Gap in Encephalitis and Acute Disseminated Encephalomyelitis through Digital Case Classification and Viral Metagenomics

Encephalitis and acute disseminated encephalomyelitis (ADEM) are often caused or triggered by viruses—but the specific pathogen commonly remains unidentified in routine care. We explored the use of viral metagenomic next-generation sequencing (mNGS) in addition to PCR testing of non-invasive stool samples to see if unbiased testing could potentially increase diagnostic yield. To identify specific clinical cases at the point of care, we took advantage of a previously published digital app allowing instant clinical case classification based on consensus case criteria, the VACC-Tool. This hospital-based prospective digital surveillance program assessed 100 pediatric patients (mean age: 11 years, range: 0.15–17.85; 49% male) with case-confirmed encephalitis and/or ADEM. Analysis of case classification at the point of care revealed that in routine care, 96% of confirmed encephalitis/ADEM cases had been missed. Overall agreement of routine care diagnoses with digital encephalitis/ADEM case classification was <50%. Also in routine care, only 13% of cases held a virus-related diagnosis, i.e., herpesvirus (n = 8) and enterovirus infection (n = 5). Use of mNGS increased the yield of virus detection by 77% (n = 23 virus hits). Specifically, mNGS identified 10 additional virus species beyond herpes- and enteroviruses. Of the additional 23 virus hits detected with mNGS, PCR confirmation was possible post hoc in 14 cases (61%). Linking digital case classification, mNGS, and PCR testing may not be feasible in routine care at this point but may help to provide hints to the pathogenesis of encephalitis/ADEM in childhood, warranting further research and exploration.

Dysregulation of the Immune System in a Natural History Study of 1299 Individuals with Down Syndrome.

Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life.

Immunoinformatics Design of Multi-Epitope Peptide-Based Vaccine Against Cyprinid Herpesvirus-3 (CyHV-3) Targeting Thymidine Kinase Proteins

The common carp Cyprinus carpio is a freshwater teleost and is among the most economically significant fishes in aquaculture throughout the world. Taxonomically, C. carpio are a complex of species including subspecies Cyprinus carpio carpio. C. carpio are now threatened by Cyprinid Herpesvirus-3 (CyHV-3), the causative agent of Koi Herpesvirus Disease (KHVD), which causes severe morbidity and mortality in ornamental koi and common carp and can infect or be transmitted by other species. Despite these devastating circumstances, effective vaccinations or other medications for the control of KHVD are not readily available. For this reason, the aim of the current study was to formulate a multi-epitope vaccine against Cyprinid Herpesvirus-3 (CyHV-3) using an immunoinformatics approach. To assess the immunodominant T- and B-cell epitopes, the CyHV-3 proteomes were employed. Following a thorough evaluation, we constructed a strategy for vaccination employing four possible epitopes selected from among each of the three relevant epitope groups: cytotoxic T-lymphocyte, helper T-lymphocyte and linear B-lymphocyte. Important qualities used in the evaluation of the resultant vaccine are that it will be highly soluble, antigenic, immunogenic and non-allergenic. Among acceptable physicochemical qualities, the anticipated structure of the vaccine bears a close resemblance to that of the original protein. Additional considerations include a robust and sustained predicted binding between the vaccine and the Toll-Like Receptor (TLR9). Simulations of molecular dynamics confirm the likelihood of a strong binding stability and structural tightness. Moreover, the computer-generated immunological simulation revealed that the vaccine, when administered to fish, should induce immune responses comparable to those in real life. Finally, codon optimization based on Escherichia coli K12 produced favorable indications of GC content and acceptably high CAI value, as applicable to the cloning vector pET28+ (a). Overall, these results show that the proposed peptide vaccine is a promising option for CyHV-3 prophylaxis.

АНАЛИЗ КЛИНИЧЕСКОГО СЛУЧАЯ ВУЛЬГАРНОЙ ПУЗЫРЧАТКИ, АССОЦИИРОВАННОЙ С ХРОНИЧЕСКОЙ ВЭБ-ИНФЕКЦИЕЙ (ГЛОССИТА, ОБУСЛОВЛЕННОГО ВЭБ)

Background. One of the autoimmune diseases is pemphigus, a chronic malignantly occurring autoimmune dermatosis accompanied by the development of blisters on the skin and mucous membranes. Isolated lesions of the SOPR occur in 10–20% of cases, complicating differential diagnosis. Numerous studies have proven the role of herpes virus infection as an aggravating factor in the course of true acantholytic pemphigus. The aim of the study was to determine the features of the clinical course of vulgar pemphigus against the background of reactivation of chronic EBV infection (glossitis caused by EBV). The clinical case of a patient with a diagnosis of “Vulgar pemphigus. Glossitis caused by the Epstein-Barr virus”. The anamnesis of the disease was carefully collected, a clinical and laboratory examination was performed with a cytological examination of a smear taken from a LITTER, a general blood test with an expanded leukocyte formula, C-reactive protein. In order to diagnose the viral load, PCR diagnostics was performed on the DNA of the herpes virus 1, 2, 4, 5 types in saliva, on the DNA of EBV in the blood, quantitatively. Specific antibodies of Ig classes M and G to EBV were determined by the ELISA method. Results. Due to the lifelong persistence of EBV in the structures of the oral cavity, its reactivation leads not only to chronic pastoral infection and the local development of the corresponding glossitis, but also, first of all, to a decrease in the level of local immunity. This fact aggravates the course of pemphigus, shortens the period of absence of relapse. The appointment of antiviral therapy at the first visit allowed to stabilize the symptoms caused by EBV, which led to positive dynamics in the course of pemphigus against the background of average dosages of prednisone in a shorter time. Conclusions. With clinical and laboratory confirmation of chronic EBV infection (glossitis caused by EBV), it is recommended to include antiviral and immunocorrective drugs, systemically and topically, in the complex treatment of pemphigus erythematosus.

Clinicoetiological profile of congenital cataracts in children: A single-center experience

Introduction: Congenital cataract is the most common treatable cause of blindness during infancy and is responsible for 5%–20% of blindness in children worldwide. Materials and Methods: It was a retrospective descriptive study analyzing the causes of congenital cataracts in infants referred to the pediatric neurology department of a tertiary care institution, in South India. Results: Thirty-two infants with congenital cataracts underwent evaluation. Thirteen (40.6%) were &lt;6 months and 19 (59.4%) beyond 6 months of age. White reflex in eyes was the primary complaint in 14 (43.8%), not looking at the caregiver in 10 (31.3%), squint in 5 (15.6%), and involuntary movement of eyeballs in 3 (9.4%) patients. Cataracts were bilateral in 26 (81.3%) and unilateral in 6 (18.7%) patients. The associated features were developmental delay in 25 (78.1%), microcephaly in 15 (46.9%), seizures in 6 (18.8%), cardiac disease in 6 (18.8%), focal deficit in 3 (9.4%), and deafness in 2 (6.3%). Neuroimaging revealed basal ganglia calcifications in 6 (18.7%), cerebral atrophy in 3 (9.4%), gliosis in parieto-occipital regions and hyperintensities in frontal regions in 2 (6.3%) children each, and hydrocephalus, Dandy–Walker malformation, thin corpus callosum, and hypomyelination in one (3.1%) each. The etiological causes were confirmed rubella syndrome in 7 (21.9%), probable rubella syndrome in 3 (9.4%), confirmed cytomegalovirus in 6 (18.8%), probable cytomegalovirus in 7 (21.9%), herpes virus infection in 1 (3.1%), combined infections in 2 (6.3%), Down syndrome in 3 (9.4%), Lowe syndrome in 1 (3.1%), and idiopathic in 2 (6.3%) patients. Conclusion: Intrauterine infections, especially cytomegaloviral and rubella infections, are the common causes for congenital cataracts in infants. Vaccination against rubella, knowledge about intrauterine infections, mode of spread, and prevention are the needs of the hour.

OUR EXPERIENCE IN THE TREATMENT OF HERPETIC KERATITIS IN CHILDREN

According to WHO, diseases caused by the herpes simplex virus occupy the second place after influenza [1,4,5]. It has been established that up to 80% of cases of temporary disability are associated with inflammatory eye diseases, 50-60 of them% they receive inpatient treatment. According to various authors, a significant place among the causes of blindness or visual impairment (10-30% of cases) belongs to keratitis and keratouveitis. Most often, this corneal disease is caused by the herpes simplex virus, which are noted in 20-57% of cases among in the adult population and in 70-80% of cases - among children [3|. But at the same time, some authors report that herpetic primary infection is usually found in young children, but in a cold form and does not require treatment. In this regard, we decided to share our experience in the treatment of herpetic keratitis in children.

Identification of Key Genes and Pathways in Oxaliplatin-Induced Neuropathic Pain Through Bioinformatic Analysis.

The mechanism of Chemotherapy-induced neuropathic pain (NP) remains obscure. This study was aimed to uncover the key genes as well as protein networks that contribute to Oxaliplatin-induced NP. Oxaliplatin frequently results in a type of Chemotherapy-induced NP that is marked by heightened sensitivity to mechanical and cold stimuli, which can lead to intolerance and discontinuation of medication. We investigated whether these different etiologies lead to similar pathological outcomes by targeting shared genetic targets or signaling pathways. Gene expression data were obtained from the Gene Expression Comprehensive Database (GEO) for GSE38038 (representing differential expression in the spinal nerve ligation model rats) and GSE126773 (representing differential expression among the Oxaliplatin-induced NP model rats). Differential gene expression analysis was performed using GEO2R. Protein-protein interaction (PPI) analysis identified 260 co-differentially expressed genes (co-DEGs). Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed three shared pathways involved in both models: Kaposi sarcoma-associated herpesvirus (KSHV) infection, Epstein-Barr virus (EBV) infection, and AGE-RAGE signaling pathway in diabetic complications. Further bioinformatics analysis highlighted eight significantly up-regulated genes in the NP group: Mapk14, Icam1, Cd44, IL6, Cxcr4, Stat1, Casp3 and Fgf2. Our results suggest that immune dysfunction, inflammation-related factors or regulating inflammation factors may also be related to Oxaliplatin-induced NP. Additionally, we analyzed a dataset (GSE145222) involving chronic compression of DRGs (CCD) and control groups. CCD model is a classic model for studying NP. We assessed these hub genes' expression levels. In contrast with the control groups, the hub genes were up-regulated in CCD groups, the difference was statistically significant, except Stat1. Our research significantly contributes to elucidating the mechanisms underlying the occurrence as well as the progression of Oxaliplatin-induced NP. We have identified crucial genes and signaling pathways associated with this condition.

Commercial human 3D corneal epithelial equivalents for modeling epithelial infection in herpes keratitis

Herpes stromal keratitis is the leading cause of infectious blindness in the western world. Infection by HSV1 is most common, but VZV and hCMV also infect the cornea. Multiple models of HSV1 corneal infection exist, but none for VZV and hCMV because of their host specificity. Here, we used commercially available 3D human corneal epithelial equivalents (HCEE) to study infection by these herpesviruses. HCEE was infected by HSV-1 and hCMV without requiring scarification and resulted in spreading infections. Spread of HSV-1 infection was rapid, while that of hCMV was slow. In contrast, infections with VZV required damage to the HCEE and did not spread. Acyclovir dramatically reduced replication of HSV-1 in this model. We conclude that highly quality-controlled, readily available HCEE is a useful model to study human-restricted herpesvirus infection of the human corneal epithelium and for screening of antiviral drugs for treating HSK in an 3D model system.

Pseudorabies virus gM and its homologous proteins in herpesviruses induce mitochondria-related apoptosis involved in viral pathogenicity.

Apoptosis is a critical host antiviral defense mechanism. But many viruses have evolved multiple strategies to manipulate apoptosis and escape host antiviral immune responses. Herpesvirus infection regulated apoptosis; however, the underlying molecular mechanisms have not yet been fully elucidated. Hence, the present study aimed to study the relationship between herpesvirus infection and apoptosis in vitro and in vivo using the pseudorabies virus (PRV) as the model virus. We found that mitochondria-dependent apoptosis was induced by PRV gM, a late protein encoded by PRV UL10, a virulence-related gene involved in enhancing PRV pathogenicity. Mechanistically, gM competitively combines with BCL-XL to disrupt the BCL-XL-BAK complex, resulting in BCL-2-antagonistic killer (BAK) oligomerization and BCL-2-associated X (BAX) activation, which destroys the mitochondrial membrane potential and activates caspase-3/7 to trigger apoptosis. Interestingly, similar apoptotic mechanisms were observed in other herpesviruses (Herpes Simplex Virus-1 [HSV-1], human cytomegalovirus [HCMV], Equine herpesvirus-1 [EHV-1], and varicella-zoster virus [VZV]) driven by PRV gM homologs. Compared with their parental viruses, the pathogenicity of PRV-ΔUL10 or HSV-1-ΔUL10 in mice was reduced with lower apoptosis and viral replication, illustrating that UL10 is a key virulence-related gene in PRV and HSV-1. Consistently, caspase-3 deletion also diminished the replication and pathogenicity of PRV and HSV-1 in vitro and in mice, suggesting that caspase-3-mediated apoptosis is closely related to the replication and pathogenicity of PRV and HSV-1. Overall, our findings firstly reveal the mechanism by which PRV gM and its homologs in several herpesviruses regulate apoptosis to enhance the viral replication and pathogenicity, and the relationship between gM-mediated apoptosis and herpesvirus pathogenicity suggests a promising approach for developing attenuated live vaccines and therapy for herpesvirus-related diseases.

T Cell Surveillance during Cutaneous Viral Infections.

The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health.

A case of acute intestinal obstruction caused by Burkitt’s lymphoma

Acute intestinal obstruction is a multifactorial disease. Its causes may be intra-abdominal adhesions, volvulus, bezoar, gallstones, foreign bodies, intestinal tumors, etc. In rare cases, acute intestinal obstruction may be associated with intussusception, which is relatively rare in adults. The purpose of this work is to demonstrate a clinical case of acute small bowel obstruction caused by Burkitt lymphoma. During treatment for a herpetic infection, the patient underwent surgical treatment — ileostomy because of acute intestinal obstruction. In the postoperative period, the patient was hospitalized due to intestinal bleeding; during diagnostic colonoscopy, intussusception of the ileum into the ascending colon was detected; diagnostic laparoscopy, laparotomy, right-sided hemicolectomy with resection of the greater omentum, restoration of intestinal continuity with elimination of the stoma,and formation of an anastomosis were performed. The material obtained intraoperatively was sent for pathomorphological examination, including the method of fluorescent hybridization, which revealed a rearrangement of the 8th chromosome in the region of localization of the MYC gene in tumor cells, and a diagnosis of Burkitt lymphoma was established. The oncological council determined the chemotherapy treatment protocol. According to the literature, Burkitt lymphoma can debut in the cutaneous form, and it is necessary to carry out a differential diagnosis, including chickenpox. There is currently no information about intestinal complications occurring in the cutaneous form of Burkitt lymphoma. It is possible that in the described case, the initially established diagnosis of herpetic infection was incorrect, and Burkitt lymphoma occurred in the cutaneous form.

Human herpesvirus 6 reactivation and disease are infrequent in chimeric antigen receptor T-cell therapy recipients

AbstractHuman herpesvirus 6B (HHV-6B) reactivation and disease are increasingly reported after chimeric antigen receptor (CAR) T-cell therapy (CARTx). HHV-6 reactivation in the CAR T-cell product was recently reported, raising questions about product and patient management. Because of overlapping manifestations with immune effector cell–associated neurotoxicity syndrome, diagnosing HHV-6B encephalitis is challenging. We provide 2 lines of evidence assessing the incidence and outcomes of HHV-6B after CARTx. First, in a prospective study with weekly HHV-6B testing for up to 12 weeks after infusion, HHV-6B reactivation occurred in 8 of 89 participants; 3 had chromosomally integrated HHV-6 and were excluded, resulting in a cumulative incidence of HHV-6B reactivation of 6% (95% confidence interval [CI], 2.2-12.5). HHV-6B detection was low level (median peak, 435 copies per mL; interquartile range, 164-979) and did not require therapy. Second, we retrospectively analyzed HHV-6B detection in the blood and/or cerebrospinal fluid (CSF) within 12 weeks after infusion in CARTx recipients. Of 626 patients, 24 had symptom-driven plasma testing, with detection in 1. Among 34 patients with CSF HHV-6 testing, 1 patient had possible HHV-6 encephalitis for a cumulative incidence of 0.17% (95% CI, 0.02-0.94), although symptoms improved without treatment. Our data demonstrate that HHV-6B reactivation and disease are infrequent after CARTx. Routine HHV-6 monitoring is not warranted.

Vaccinoprophylaxis of infections and activity of immuno-inflammatory rheumatic diseases: pro et contra

In modern conditions, patients with immuno-inflammatory rheumatic diseases (IIRD) are at significant risk of influenza, pneumococcal and herpes viral infections, as well as COVID-19, in some cases fatal. The most effective way to prevent infectious diseases and reduce mortality from them is vaccination, which is recommended in the inactive phase of IIRD. However, a number of patients with IIRD have a refractory course of the disease, and achieving remission in them turns out to be a difficult task, and therefore the problem of vaccination of such patients against the background of an active inflammatory process is very relevant. The review analyzes data on the use of vaccine prophylaxis for the above infections in the active phase of IIRD. In the vast majority of cases, vaccination was safe and did not lead to an exacerbation of IIRD or the development of new autoimmune phenomena.

Progression of herpesvirus infection remodels mitochondrial organization and metabolism.

Viruses target mitochondria to promote their replication, and infection-induced stress during the progression of infection leads to the regulation of antiviral defenses and mitochondrial metabolism which are opposed by counteracting viral factors. The precise structural and functional changes that underlie how mitochondria react to the infection remain largely unclear. Here we show extensive transcriptional remodeling of protein-encoding host genes involved in the respiratory chain, apoptosis, and structural organization of mitochondria as herpes simplex virus type 1 lytic infection proceeds from early to late stages of infection. High-resolution microscopy and interaction analyses unveiled infection-induced emergence of rough, thin, and elongated mitochondria relocalized to the perinuclear area, a significant increase in the number and clustering of endoplasmic reticulum-mitochondria contact sites, and thickening and shortening of mitochondrial cristae. Finally, metabolic analyses demonstrated that reactivation of ATP production is accompanied by increased mitochondrial Ca2+ content and proton leakage as the infection proceeds. Overall, the significant structural and functional changes in the mitochondria triggered by the viral invasion are tightly connected to the progression of the virus infection.

Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto's thyroiditis in a group of Iranian patients.

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

Clinical experience in the use of local antiviral therapy for glossitis caused by the herpes virus type IV

Herpetic infections are one of the most common anthroponotic diseases. The prevalence of herpes virus types, their combined manifestation in the body of one person, as well as the increase in the number of people with secondary immunodeficiency make the problem of diagnosis and treatment of herpes-associated diseases the most urgent [1,2].As is known, herpes virus type IV (Epstein-Barr, EBV) is one of the frequently encountered members of the herpesvirus family [3]. According to the researches of many authors, by the age of 45 they have infected up to 100% of the world's population [4,5]. Persisting in the tissues of the mucous membrane of the oral cavity (lymphoepithelial pharyngeal ring of Pirogov-Valdeier, stroma of salivary glands, epithelial cells), reactivation of the virus occurs in the case of a decrease in immunity. [8,9]. At the same time, the number of diseases caused by EBV increases annually and depends on the phase of virus activity [10,11].One of the relatively "young" EBV-associated diseases is the corresponding glossitis, the clinical and laboratory characteristics of which are poorly presented in the literature. For this reason, the therapy of oral manifestations of chronic EBV infection is considered from the position of treating infectious mononucleosis [6,7], which is ineffective. Ignorance of dentists about the reliable clinical and laboratory signs of EBV caused by glossitis leads to incorrect diagnosis and inadequate treatment, generalization of infection, and the appearance of opportunistic diseases.

Polyphenols from Maackia amurensis Heartwood Protect Neuronal Cells from Oxidative Stress and Prevent Herpetic Infection.

Here, we continued the investigation of anti-HSV-1 activity and neuroprotective potential of 14 polyphenolic compounds isolated from Maackia amurensis heartwood. We determined the absolute configurations of asymmetric centers in scirpusin A (13) and maackiazin (10) as 7R,8R and 1″S,2″S, respectively. We showed that dimeric stilbens maackin (9) and scirpusin A (13) possessed the highest anti-HSV-1 activity among polyphenols 1-14. We also studied the effect of polyphenols 9 and 13 on the early stages of HSV-1 infection. Direct interaction with the virus (virucidal activity) was the main mechanism of the antiviral activity of these compounds. The neuroprotective potential of polyphenolic compounds from M. amurensis was studied using models of 6-hydroxydopamine (6-OHDA)-and paraquat (PQ)-induced neurotoxicity. A dimeric stilbene scirpusin A (13) and a flavonoid liquiritigenin (6) were shown to be the most active compounds among the tested polyphenols. These compounds significantly increased the viability of 6-OHDA-and PQ-treated Neuro-2a cells, elevated mitochondrial membrane potential and reduced the intracellular ROS level. We also found that scirpusin A (13), liquiritigenin (6) and retusin (3) considerably increased the percentage of live Neuro-2a cells and decreased the number of early apoptotic cells. Scirpusin A (13) was the most promising compound possessing both anti-HSV-1 activity and neuroprotective potential.

Herpesvirus Infection of Endothelial Cells as a Systemic Pathological Axis in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Understanding the pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is critical for advancing treatment options. This review explores the novel hypothesis that a herpesvirus infection of endothelial cells (ECs) may underlie ME/CFS symptomatology. We review evidence linking herpesviruses to persistent EC infection and the implications for endothelial dysfunction, encompassing blood flow regulation, coagulation, and cognitive impairment-symptoms consistent with ME/CFS and Long COVID. This paper provides a synthesis of current research on herpesvirus latency and reactivation, detailing the impact on ECs and subsequent systemic complications, including latent modulation and long-term maladaptation. We suggest that the chronicity of ME/CFS symptoms and the multisystemic nature of the disease may be partly attributable to herpesvirus-induced endothelial maladaptation. Our conclusions underscore the necessity for further investigation into the prevalence and load of herpesvirus infection within the ECs of ME/CFS patients. This review offers conceptual advances by proposing an endothelial infection model as a systemic mechanism contributing to ME/CFS, steering future research toward potentially unexplored avenues in understanding and treating this complex syndrome.

Seroprevalence of Cytomegalovirus, Epstein-barr Virus and Herpes Simplex Viruses in Children Born HIV Positive at the Yaounde University Teaching Hospital, Cameroon

Background: Cameroon is a country located in sub-Saharan Africa, which is an area endemic to herpesviridae family, there is very little data on the herpes virus infections epidemiology, especially associated with HIV infection. Aims: The aim of our study was to determine the seroprevalence of four herpes viruses that are cytomegalovirus (CMV), Epstein-Barr virus (EBV), Herpes Simplex virus 1 (HSV-1) and 2 (HSV-2) in HIV-positive patients in Yaoundé University Teaching Hospital. Methodology: the study was prospective cross-sectional and took place at Yaounde University Teaching Hospital and Department of Microbiology, Faculty of Sciences, University of Yaounde I, between November 2020 and April 2021. We included consecutively 74 on children living with HIV born HIV positive, on antiretroviral treatment (23 men, 51 women; age range 3-19 years), and whose medical file was complete and available within the ATC. IgG/IgM antibodies against HSV-1, HSV-2, CMV, and IgM against EBV were qualitatively determined by Rapid Diagnostic Tests, for the detection of these pathogens. The statistical analysis was done using IBM SPSS version 22.0, the Fisher exact and the Khi-sqaure tests to compare qualitative variables between groups, while on the other hand, we used the Mann-Whitney test to compare quantitative variables. All P values below 0.05 were considered significant. Results: A total of 74 participants were enrolled in the study with a female predominance of 68.92% (n=51/74). The average age of our serie was 9.05±5.09 years, and a majority of participants was under 10 years old (56.76%, n=42/74). HSV-1, HSV-2, EBV and CMV Seroprevalences were 93.24%, 93.24%, 22.97% and 12.2% respectively. Other parameters such as sex, age, stage of disease, smoking and alcohol consumption were significantly associated with the seropositivity of these herpesviridae. Conclusion: Despite the absence for most of the clinical manifestations related to HSV-1 and HSV-2, it was strong to note a high circulation of those virus in HIV infected patients, mainly in bi and tri co-infections.