Herpesvirus Infection Research Articles

PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants

Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCγ2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAID). Since describing these conditions, many PLCG2 variants of uncertain significance have been identified by clinical sequencing of patients with diverse features of ID. We sought to functionally classify PLCG2 variants and explore known and novel genotype-function-phenotype relationships. Clinical data from patients with PLCG2 variants were obtained via standardized questionnaire. PLCG2 variants were generated by mutagenesis of enhanced green fluorescent protein (EGFP)-PLCG2 plasmid, which was overexpressed in Plcg2-deficient DT-40 B cells. B-cell receptor-induced calcium flux and extracellular signal-regulated kinase phosphorylation were assayed by flow cytometry. In some cases, stimulation-induced calcium flux was also measured in primary patient cells. Three-fourths of PLCG2 variants produced functional alteration of B-cell activation, invitro. Thirteen variants led to gain of function (GOF); however, most functional variants defined a new class of PLCG2 mutation, monoallelic loss of function (LOF). Susceptibility to infection and autoinflammation were common with both GOF and LOF variants, whereas a new phenotypic cluster consisting of humoral immune deficiency, autoinflammation, susceptibility to herpesvirus infection, and natural killer cell dysfunction was observed in association with multiple heterozygous LOF variants detected in both familial and sporadic cases. In some cases, PLCG2 variants produced greater effects in natural killer cells than in B cells. This work expands the genotypic and phenotypic associations with functional variation in PLCG2, including a novel form of ID in carriers of heterozygous loss of PLCG2 function. It also demonstrates the need for more diverse assays for assessing the impact of PLCG2 variants on human disease.

Positive effects of recombinant interferon α2b on the phenotype of CD16<sup>+</sup>INFα/βR1<sup>-</sup>CD119<sup>+</sup>, CD16<sup>+</sup>INFα/βR1<sup>+</sup>CD119<sup>-</sup> neutrophil granulocyte subset in patients with post-COVID syndrome and herpesvirus infections

Post-COVID syndrome (PCS) is a multisystem inflammatory condition with manifestations of chronic fatigue syndrome (CFS) and cognitive disorders (CD), along with reactivation of chronic herpesvirus infections (HVI). The PCS manifestations require studying the molecular mechanisms associated with the production of IFN and receptor functions of neutrophil granulocytes (NG), which is relevant and promotes the search for immunotherapeutic strategies in patients with PCS. Our objective was to study the in vitro effects of recombinant interferon α2b (recIFNα2b) on the phenotype of CD16+IFNα/βR1-CD119+, CD16+IFNα/ βR1+CD119+ subsets and functional activity of NG in patients with post-COVID syndrome and herpesvirus infections. Materials and methods: 45 patients (24-60 years old) with PCS and HVI (HSV 1, EBV, HHV6, CMV) comprised the study group 1 (SG1). A questionnaire was conducted to assess the severity of PCS symptoms using a point scale. We performed a study of the content and phenotype of NG subsets, i.e., the CD16+IFNα/βR1-CD119+, CD16+IFNα/βR1+CD119-, CD16+IFNα/βR1+CD119+ subpopulation, phagocytic and NADPH oxidase function of NG before and after in vitro incubation with recIFNα2b (50 IU/ µL, for 60 min, at 37 °C) in the study group 1a (SG1a). The comparison group (CG) of 30 volunteers examined during the pre-COVID period. Results: We revealed more pronounced clinical manifestations of CFS and CD in SG1 patients with mixed HVI, than in mono-HVI cases. Increased expression density of all receptors was registered on CD16+IFNα/βR1+CD119-NG and CD16+IFNα/βR1-CD119+ NG, thus suggesting the NG activation with initiation of cytotoxicity or NETosis, a decrease in phagocytic function and intensity of NADPH oxidase activity with depletion of NG reserve capacity in SG1. We have obtained some data on the positive effect of recIFNα2b in vitro (SG1a), e.g., decreased CD16 expression density and enhancement of IFNα/βR1 receptor expression in the CD16+IFNα/βR1+CD119- subset. In the CD16+IFNα/βR1-CD119+ subset, we have found persistence of increased MFI CD16 and MFI CD119 receptors, restoration of defective NG phagocytic function and reduced excessive activity of NADPH oxidases. Conclusion: The positive effects of the recIFNα2b influence on deficient function of NG in PCS patients suggest an oppoptunity of using immunotherapy with a recIFNα2b-based drug, combined with highly active antioxidants for treatment of various PCS manifestations including CFS, CD, HVI, thus, probably, ensuring adequate functioning of antiviral and regulatory mechanisms of the immune system.

Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence.

Herpesviruses have evolved a series of abilities involved in the process of host infection that are conducive to virus survival and adaptation to the host, such as immune escape, latent infection, and induction of programmed cell death for sustainable infection. The herpesvirus gene UL24 encodes a highly conserved core protein that plays an important role in effective viral infection. The UL24 protein can inhibit the innate immune response of the host by acting on multiple immune signaling pathways during virus infection, and it also plays a key role in the proliferation and pathogenicity of the virus in the later stage of infection. This article reviews the mechanism by which the UL24 protein mediates herpesvirus immune escape and its effects on viral proliferation and virulence by influencing syncytial formation, DNA damage and the cell cycle. Reviewing these studies will enhance our understanding of the pathogenesis of herpesvirus infection and provide evidence for new strategies to combat against viral infection.

Network pharmacology and molecular docking to explore the mechanism of Sheng Xue Bao mixture against iron deficiency anemia.

Based on network pharmacology and molecular docking, we investigated the mechanism of action of Sheng Xue Bao mixture (SXBM) in treating iron deficiency anemia (IDA). We screened the HERB and traditional Chinese medicine systems pharmacology database and analysis platform databases to identify the active ingredients and targets of SXBM. The targets associated with "iron deficiency anemia" were collected from GeneCards, TTD, and OMIM databases. A component-target interaction network was constructed using Cytoscape 3.8.2. The protein-protein interaction network of candidate targets was generated using the STRING database and visualized with Cytoscape 3.8.2 software. Core modules obtained from clustering analysis were subjected to Gene Ontology and Kyoto encyclopedia of genes and genomes enrichment analysis. Finally, molecular docking validation of key targets and active components was performed using Autodock Vina software. A total of 174 active components and 111 genes were identified as potential active components and targets for IDA treatment, including quercetin, kaempferol, luteolin, beta-sitosterol, and other flavonoids as main active components. Gene Ontology enrichment analysis show that interleaved genes are enriched in 2328 biological processes, 71 cellular component expression processes, and 157 molecular function processes. Kyoto encyclopedia of genes and genomes analysis mainly envolved Prostate cancer, Hepatitis B, Kaposi sarcoma-associated herpesvirus infection, Endocrine resistance, Lipid and atherosclerosis, Central carbon metabolism in cancer, Human cytomegalovirus infection and HIF-1 signaling pathway. STAT3, SRC, PIK3R1, and GRB2 were selected as core targets. The molecular docking results demonstrated strong interactions between key components and their respective target proteins. Network pharmacological analysis suggested that SXBM could treat IDA by regulating various biological processes and related signaling pathways. It laid the foundation for further elucidating the molecular mechanism of SXBM treatment of IDA.

Prevalence, Incidence, and Predictors of Kaposi Sarcoma-Associated Herpesvirus Infection Among Young Men Who Have Sex With Men in the Southern United States.

Kaposi sarcoma (KS) continues to cause substantial morbidity and mortality in populations at risk in the southern United States. Utilizing biospecimens from the Houston site of the Young Men's Affiliate Project, 351 men who have sex with men had blood tested for KS-associated herpesvirus (KSHV) IgG. Seroprevalence, seroconversion between time points, and demographic and clinical correlates were measured. KSHV prevalence was 36.7% and incidence was 8.9 per 100 person-years. Furthermore, prevalence and incidence were higher among Black individuals, people living with HIV, and those with a history of syphilis. Further research on KSHV risk may improve health disparities in KS diagnosis and outcomes.

Human PLCG2 haploinsufficiency results in a novel natural killer cell immunodeficiency

Although most individuals effectively control herpesvirus infections, some suffer from severe and/or recurrent infections. Asubset of these patients possess defects in natural killer (NK) cells, lymphocytes that recognize and lyse herpesvirus-infected cells; however, the genetic etiology is rarely diagnosed. PLCG2 encodes a signaling protein in NK-cell and B-cell signaling. Dominant-negative or gain-of-function variants in PLCG2 cause cold urticaria, antibody deficiency, and autoinflammation. However, loss-of-function variants and haploinsufficiency have not been reported todate. The investigators aimed to identify the genetic cause of NK-cell immunodeficiency in 2 families and herein describe the functional consequences of 2 novel loss-of-function variants in PLCG2. The investigators employed whole-exome sequencing in conjunction with mass cytometry, microscopy, functional assays, and a mouse model of PLCG2 haploinsufficiency to investigate 2 families with NK-cell immunodeficiency. The investigators identified novel heterozygous variants in PLCG2 in 2 families with severe and/or recurrent herpesvirus infections. Invitro studies demonstrated that these variants were loss of function due to haploinsufficiency with impaired NK-cell calcium flux and cytotoxicity. In contrast to previous PLCG2 variants, B-cell function remained intact. Plcg2+/- mice also displayed impaired NK-cell function with preserved B-cell function, phenocopying human disease. PLCG2 haploinsufficiency represents a distinct syndrome from previous variants characterized by NK-cell immunodeficiency with herpesvirus susceptibility, expanding the spectrum of PLCG2-related disease.

Management of Orofacial Herpes (Visarpa) Through Ayurvedic Approach

Herpes Simplex infection of mouth and face is known as ‘Oro Facial Herpes Simplex (cold sores). The incident rate of herpes viral infection is found to be around 7-14% in adolescents in India. It is caused by herpes simplex virus type 1 (HSVL). Oro facial herpes simplex causes inflamed and localized blisters that pop, weep and form crusts. At initial stage it shows symptoms like redness, swelling, heat and itching along with pain. Over a period of time the blisters leak out and become sores. According to Ayurveda literature, this disease can be co-related with ‘Pittaja Visarpa.’ Here presenting a case report of 52-year-old male with sudden onset of painful blisters, redness and burning pain on the jaw region. The patient was managed with Sutshekhar rasa, Avipattikar churna as oral medication and Jatyadi oil (Sheath Veda) and Khas Anantmool Ayurvedic cream (Sheath Veda) for local application over the jaw region. The patient showed improvement within two weeks and got significant relief over a month.

Reasons for hospitalisation in youth with type 1 diabetes, 2010-2019.

To determine the incidence of hospitalisation for all diagnoses among Australian youth with type 1 diabetes. We linked Australians aged under 20 years with type 1 diabetes on the National Diabetes Services Scheme (n = 45,685) to hospital admission data from 2010 to 2019. We determined relative risks (RR) of hospitalisation among those with type 1 diabetes in the states of Victoria and Queensland (n = 21,898) compared to the general population for 2010-2017 using Poisson regression. Australian youth with type 1 diabetes had increased risk for almost all reasons for hospitalisation compared to the general population, especially infections such as anogenital herpesviral infections (RR 54.83, 95% CI 33.21-90.53), and mental health disorders including personality disorders (RR 9.70, 95% CI 8.02-11.72). Among those with type 1 diabetes, over 60% of hospitalisations were directly related to diabetes, almost half of which were for ketoacidosis. Approximately 15% of ketoacidosis admissions occurred within 3 months of diabetes diagnosis. One quarter of those with admissions for ketoacidosis were readmitted for ketoacidosis within 12 months. Residence in areas of high socio-economic disadvantage was an independent risk factor for admission and readmission for ketoacidosis. Youth with type 1 diabetes are susceptible to a wide range of complications. Clinicians should consider screening and prevention for conditions such as infections and mental health disorders. Targeted support and education around glycaemic management should be considered in those at high risk for ketoacidosis admission including those living in areas of high socio-economic disadvantage.

Herpesvirus latent infection promotes stroke via activating the OTUD1/NF-κB signaling pathway.

Our study aimed to reveal the molecular mechanisms underlying the regulation of cerebral infarction by herpes virus latency infection via the OTUD1/NF-κB signaling pathway using evidence-based medicine Meta-analysis and bioinformatics analysis. We conducted a Meta-analysis by searching Pubmed, Embase, and Web of Science databases to evaluate the correlation between herpes virus infection and increased risk of cerebral infarction. We obtained wild-type or mutant herpes virus latent infection-related brain tissue datasets from the GEO database and performed differential analysis to identify differentially expressed genes (DEGs) in the brain tissue after herpes virus latent infection. We further conducted WGCNA co-expression analysis on the cerebral infarction-related datasets from the GEO database to obtain key module genes and intersect them with the DEGs. We used ROC curve analysis to identify the key gene OTUD1 for predicting the occurrence of cerebral infarction and combined correlation and pathway enrichment analyses to identify the downstream pathways regulated by OTUD1. Our meta-analysis revealed that herpes virus infection is associated with an increased risk of cerebral infarction. By integrating the differential analysis and WGCNA co-expression analysis of GEO chip data, we identified three key genes mediating cerebral infarction after herpes virus latent infection. ROC curve analysis identified the key gene OTUD1, and the correlation and pathway enrichment analyses showed that OTUD1 regulates the NF-κB signaling pathway to mediate cerebral infarction. Herpes virus latent infection promotes cerebral infarction by activating the OTUD1/NF-κB signaling pathway.

Features of damage to the nervous system in herpesvirus infections

Actuality. Herpesvirus diseases are characterized by a wide distribution, polymorphism of clinical manifestations and severity of the course up to the development of lethal outcomes. The purpose of the study: to identify the features of the damage to the nervous system in herpes infections in modern conditions. Materials and methods. Under observation there were 60 patients with lesions of the nervous system due to herpesvirus infections, hospitalized in the Infectious Clinical Hospital in 2015-2021. Results and discussion. The analysis of the main clinical and laboratory parameters was carried out and the features of the damage to the nervous system in herpesvirus infections were established. Conclusion. The results of the study showed that patients with VZV infection prevailed among all patients — 78.3%. The range of lesions of the nervous system was presented in the form of serous meningitis (48.3%), meningoencephalitis (43.3%), encephalitis (8.4%).

Interferon-λ Activates a Differential Response in Peripheral Neurons That Is Effective against Alpha Herpesvirus Infections.

Alpha herpesviruses (α-HV) infect host mucosal epithelial cells prior to establishing a life-long latent infection in the peripheral nervous system. The initial spread of viral particles from mucosa to the nervous system and the role of intrinsic immune responses at this barrier is not well understood. Using primary neurons cultured in compartmentalized chambers, prior studies performed on Pseudorabies virus (PRV) have demonstrated that type I and type II interferons (IFNs) induce a local antiviral response in axons via distinct mechanisms leading to a reduction in viral particle transport to the neuronal nucleus. A new class of interferons known as type III IFNs has been shown to play an immediate role against viral infection in mucosal epithelial cells. However, the antiviral effects of type III IFNs within neurons during α-HV infection are largely unknown. In this study, we focused on elucidating the antiviral activity of type III IFN against PRV neuronal infection, and we compared the interferon-stimulated gene (ISGs) induction pattern in neurons to non-neuronal cells. We found that IFN pre-exposure of both primary neurons and fibroblast cells significantly reduces PRV virus yield, albeit by differential STAT activation and ISG induction patterns. Notably, we observed that type III IFNs trigger the expression of a subset of ISGs mainly through STAT1 activation to induce an antiviral state in primary peripheral neurons.

Deucravacitinib: a novel TYK2 inhibitor for the treatment of moderate-to-severe psoriasis.

Deucravacitinib is a first-in-class tyrosine kinase 2 (TYK2) inhibitor recently approved for the treatment of adults with moderate-to-severe plaque psoriasis. To discuss the mechanism of action, efficacy, safety, and real-world applications of deucravacitinib for the treatment of psoriasis. Literature on the mechanism of action of deucravacitinib is reviewed. The pivotal clinical studies and long-term extension studies for deucravacitinib are also examined. Deucravacitinib is a novel oral TYK2 inhibitor that binds to the regulatory domain of TYK2, a Janus kinase. By inhibiting TYK2, deucravacitinib interferes with signaling of IL-23, IL-12, and type I interferons, cytokines believed to play important roles in psoriasis pathogenesis. Nearly 60% of patients achieve PASI 75 at 16 weeks of treatment; efficacy improves over 24 weeks and is maintained through 2 years of continuous treatment. In a head-to-head comparison, deucravacitinib efficacy was superior to apremilast, an older yet commonly used oral PDE4 inhibitor approved for the treatment of psoriasis. Of note, patients with moderate-to-severe plaque psoriasis with concomitant involvement of the scalp, nails, and/or palms/soles demonstrated good improvement in these high impact areas. Deucravacitinib has an acceptable safety profile and is generally well-tolerated. Small increases in reactivation of herpesvirus infections, including herpes simplex outbreaks, have been reported. Tuberculosis evaluation, but no other blood tests, is recommended prior to initiation of deucravacitinib. Monitoring of triglyceride levels should be conducted for high-risk patients according to local guidelines. Deucravacitinib is an effective, safe, and well-tolerated novel oral medication for adults with moderate-to-severe plaque psoriasis.

Hypoxia and hypoxia-inducible factors in Kaposi sarcoma-associated herpesvirus infection and disease pathogenesis.

Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma and several other tumors and hyperproliferative diseases seen predominantly in human immunodeficiency virus-infected and other immunocompromised persons. There is an increasing body of evidence showing that hypoxia and hypoxia-inducible factors (HIFs) play important roles in the biology of KSHV and in the pathogenesis of KSHV-induced diseases. Hypoxia and HIFs can induce lytic activation of KSHV and KSHV can in turn lead to a hypoxic-like state in infected cells. In this review, we describe the complex interactions between KSHV biology, the cellular responses to hypoxia, and the pathogenesis of KSHV-induced diseases. We also describe how interference with HIFs can lead to decreased tumor growth and/or death of infected cells and KSHV-induced tumors. Finally, we show how these observations may lead to novel strategies for the treatment of KSHV-induced diseases.

A New Sturgeon Herpesvirus from Juvenile Lake Sturgeon Acipenser fulvescens Displaying Epithelial Skin Lesions.

Herpesvirus infections of sturgeon pose a potential threat to sturgeon culture efforts worldwide. A new epitheliotropic herpesvirus named Acipenser herpesvirus 3 (AciHV-3) was detected in hatchery-reared Lake Sturgeon Acipenser fulvescens displaying skin lesions in central Canada. The growths were discovered in the fall, reached average prevalence levels of 0.2-40% and eventually regressed. No unusual mortality was observed. The cellular changes within the lesions included epithelial hyperplasia and were reminiscent of other herpesvirus infections. The virus was not evident in lesions examined by electron microscopy. Skin tissue homogenates from symptomatic sturgeon produced atypical cytopathic effects on a primary Lake Sturgeon cell line, and next-generation sequence analysis of the DNA samples revealed the presence of an alloherpesvirus. A new genotyping PCR assay targeting the major capsid protein sequence detected AciHV-3 in symptomatic Lake Sturgeon as well as other apparently healthy sturgeon species. Bayesian inference of phylogeny reconstructed with a concatenation of five alloherpesvirus core proteins revealed a new Alloherpesviridae lineage isomorphic with a new genus. The presence of AciHV-3 homologs in cell lines and sturgeon sequence datasets, low sequence divergence among these homologs and branching patterns within the genotyping phylogeny provide preliminary evidence of an endogenous virus lifestyle established in an ancestral sturgeon.

Helicase-independent function of RIG-I against murine gammaherpesvirus 68 via blocking the nuclear translocation of viral proteins

Innate immunity is the first line of defense against viral pathogens. Retinoic Acid-Inducible Gene 1 (RIG-I) is a pattern recognition receptor that recognizes virus-associated double-stranded RNA and initiates the interferon responses. Besides signal transduction, RIG-I exerts direct antiviral functions to displace viral proteins on dsRNA via its Helicase activity. Nevertheless, this effector-like activity of RIG-I against herpesviruses remains largely unexplored. It has been previously reported that herpesviruses deamidate RIG-I, resulting in the abolishment of its Helicase activity and signal transduction. In this study, we discovered that RIG-I possessed signaling-independent antiviral activities against murine gamma herpesviruses 68 (γHV68, murid herpesvirus 4). Importantly, a Helicase-dead mutant of RIG-I (K270A) demonstrated comparable inhibition on herpesviruses lytic replication, indicating that this antiviral activity is Helicase-independent. Mechanistically, RIG-I bound the Replication and Transcription Activator (RTA) and diminished its nuclear localization to repress viral transcription. We further demonstrated that RIG-I blocked the nuclear translocation of ORF21 (Thymidine Kinase), ORF75c (vGAT), both of which form a nuclear complex with RTA and RNA polymerase II (Pol II) to facilitate viral transcription. Moreover, RIG-I retained ORF59 (DNA processivity factor) in the cytoplasm to repress viral DNA replication. Altogether, we illuminated a previously unidentified, Helicase-independent effector-like function of RIG-I against γHV68, representing an exquisite host strategy to counteract viral manipulations on innate immune signaling. ImportanceRetinoic acid-inducible gene I (RIG-I), a member of DExD/H box RNA helicase family, functions as a key pattern recognition receptor (PRR) responsible for the detection of intracellular double-stranded RNA (dsRNA) from virus-infected cells and induction of type I interferon (IFN) responses. Nevertheless, our understanding of the helicase-independent effector-like activity of RIG-I against virus infection, especially herpesvirus infection, remains largely unknown. Herein, by deploying murine gamma herpesviruses 68 (γHV68) as a model system, we demonstrated that RIG-I possessed an interferon and helicase-independent antiviral activity against γHV68 via blocking the nuclear trafficking of viral proteins, which concomitantly repressed the viral early transcription and genome replication thereof. Our work illuminates a previously unidentified antiviral strategy of RIG-I against herpesvirus infection.

Constrictive Pericarditis induced by Human Herpes Virus Infection: A Case Report

Constrictive pericarditis represents a severe diastolic heart failure secondary to an inelastic and poorly compliant pericardium mediated by inflammation and fibrosis. It shows relative regional and temporal differences with respect to the etiologies.

COVID-19: A novel holistic systems biology approach to predict its molecular mechanisms (in vitro) and repurpose drugs.

COVID-19 strangely kills some youth with no history of physical weakness, and in addition to the lungs, it may even directly harm other organs. Its complex mechanism has led to the loss of any significantly effective drug, and some patients with severe forms still die daily. Common methods for identifying disease mechanisms and drug design are often time-consuming or reductionist. Here, we use a novel holistic systems biology approach to predict its molecular mechanisms (in vitro), significant molecular relations with SARS, and repurpose drugs. We have utilized its relative phylogenic similarity to SARS. Using the available omics data for SARS and the fewer data for COVID-19 to decode the mechanisms and their significant relations, We applied the Cytoscape analyzer, MCODE, STRING, and DAVID tools to predict the topographically crucial molecules, clusters, protein interaction mappings, and functional analysis. We also applied a novel approach to identify the significant relations between the two infections using the Fischer exact test for MCODE clusters. We then constructed and analyzed a drug-gene network using PharmGKB and DrugBank (retrieved using the dgidb). Some of the shared identified crucial molecules, BPs and pathways included Kaposi sarcoma-associated herpesvirus infection, Influenza A, and NOD-like receptor signaling pathways. Besides, our identified crucial molecules specific to host response against SARS-CoV-2 included FGA, BMP4, PRPF40A, and IFI16. We also introduced seven new repurposed candidate drugs based on the drug-gene network analysis for the identified crucial molecules. Therefore, we suggest that our newly recommended repurposed drugs be further investigated in Vitro and in Vivo against COVID-19.

Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

Lives of Skin Lesions in Monkeypox: Histomorphological, Immunohistochemical, and Clinical Correlations in a Small Case Series.

Monkeypox (mpox), a former rare viral zoonosis, has increasingly made it into the public eye since the major outbreak that started in May 2022. Mpox presents with skin lesions that change over time and go through different stages (macular, papular, pustular, and early and late ulceration). In this study, we evaluated skin biopsies of all stages. Therefore, five biopsies from four patients were analyzed histologically, immunohistochemically with anti-Vaccinia virus antibodies, and electron-microscopically. Notably, the early macular stage only showed subtle viropathic changes; it did not express of Orthopoxvirus proteins in immunohistochemistry and therefore can easily be missed histologically. In later stages, immunohistochemistry with anti-Vaccinia virus antibodies might be useful to distinguish mpox from differential diagnoses such as herpes virus infections. In the ulcerative stages, the identified occlusive vasculopathic changes could be an explanation for the severe pain of the lesions reported by some patients. Despite the small number of samples examined, our analysis suggests that the histological findings of mpox are highly dependent on the stage of the biopsied lesion. Therefore, knowledge of all different stages of histology is necessary to reliably diagnose mpox histologically, especially when molecular testing is not available.

Prevalence of Cyprinid herpesvirus 3 and ORF150 genomic variations in carp populations of Indonesia

Cyprinid herpesvirus-3 (CyHV-3) is the etiological agent of koi herpesvirus disease (KHVD) in common and koi carp farming. This highly contagious pathogen has a 295-kb genome that harbours 156 open reading frames. Recent in vitro experimental evolution studies highlighted strong dynamics of genomic structural variations (SVs), in particular in the region of ORF150, an ORF potentially involved in virus multiplication and host inflammatory response. Among these SVs, a 1363-bp deletion could be associated with a loss of virulence. The present study aimed at investigating the genomic variations in the ORF150 region, and especially the deletion, in viruses isolated from carp populations of Indonesia. A screening of 236 fish from 43 different farms revealed a high prevalence of CyHV-3 (nearly 70%), both in symptomatic and asymptomatic common carp. However, in contrast with the results obtained in vitro, long read sequencing of the ORF150 region revealed a low level of genetic variations and the absence of the 1363-pb deletion. The complex interactions between the virus, the environment and the host, particularly the immune system, probably play an important role in this reduced variability.