Herpesvirus Family Research Articles

The evaluation of the effectiveness of bacterial lysate in preoperative preparation of children with adenotonsillar pathology

In childhood, the occurrence and steady growth of diseases of the nasopharyngeal tonsils, often acquiring a chronic course and occurring with exacerbations and complications, is facilitated by a number of factors. Etiological factors of adenotonsillar diseases in children are both bacterial and viral pathogens, among which respiratory viruses are among the most significant. Herpes virus infections (HVI) play an important role in the development of chronic upper respiratory tract pathology, especially in the cohort of frequently ill children. Representatives of the herpes virus family are characterized by lymphotropic action, long-term persistence in the body, and a tendency to reproduce in cells, leading to a violation of the immune status. The incidence of relapses in the postoperative period during surgical interventions in the ENT organs in children remains high. Herpesvirus etiology of recurrent infectious and inflammatory diseases of the URT (upper respiratory tract) is the leading factor in the ineffectiveness of tonsillotomy, adenotomy, and repeated proliferation of lymphoid tissue in the postoperative period in preschool children. The use of a drug from the group of bacterial lysates before surgery is justified in the treatment of frequently and long-term ill children with adenotonsillar hypertrophy.

An In Silico Approach to Discover Efficient Natural Inhibitors to Tie Up Epstein–Barr Virus Infection

Epstein–Barr virus (EBV), also known as human herpesvirus 4, is a member of the herpes virus family. EBV is a widespread virus and causes infectious mononucleosis, which manifests with symptoms such as fever, fatigue, lymphadenopathy, splenomegaly, and hepatomegaly. Additionally, EBV is associated with different lymphocyte-associated non-malignant, premalignant, and malignant diseases. So far, no effective treatment or therapeutic drug is known for EBV-induced infections and diseases. This study investigated natural compounds that inhibit EBV glycoprotein L (gL) and block EBV fusion in host cells. We utilised computational approaches, including molecular docking, in silico ADMET analysis, and molecular dynamics simulation. We docked 628 natural compounds against gL and identified the four best compounds based on binding scores and pharmacokinetic properties. These four compounds, with PubChem CIDs 4835509 (CHx-HHPD-Ac), 2870247 (Cyh-GlcNAc), 21206004 (Hep-HHPD-Ac), and 51066638 (Und-GlcNAc), showed several interactions with EBV gL. However, molecular dynamics simulations indicated that the protein–ligand complexes of CID: 4835509 (CHx-HHPD-Ac) and CID: 2870247 (Cyh-GlcNAc) are more stable than those of the other two compounds. Therefore, CIDs 4835509 and 2870247 (Cyh-GlcNAc) may be potent natural inhibitors of EBV infection. These findings can open a new way for effective drug design against EBV and its associated infections and diseases.

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.

Long-read transcriptomics of Ostreid herpesvirus 1 uncovers a conserved expression strategy for the capsid maturation module and pinpoints a mechanism for evasion of the ADAR-based antiviral defence

Abstract Ostreid herpesvirus 1 (OsHV-1), a member of the family Malacoherpesviridae (order Herpesvirales), is a major pathogen of bivalves. However, the molecular details of the malacoherpesvirus infection cycle and its overall similarity to the replication of mammalian herpesviruses (family Orthoherpesviridae) remain obscure. Here, to gain insights into the OsHV-1 biology, we performed long read sequencing of infected blood clams, Anadara broughtonii, which yielded over one million OsHV-1 long reads. This data enabled the annotation of the viral genome with 78 gene units and 274 transcripts, of which 67 were polycistronic mRNAs, 35 ncRNAs and 20 natural antisense transcripts (NATs). Transcriptomics and proteomics data indicate preferential transcription and independent translation of the capsid scaffold protein as an OsHV-1 capsid maturation protease isoform. The conservation of this transcriptional architecture across Herpesvirales likely indicates its functional importance and ancient origin. Moreover, we traced RNA editing events using short read sequencing and supported the presence of inosine nucleotides in native OsHV-1 RNA, consistent with the activity of ADAR1. Our data suggests that, whereas RNA hyper-editing is concentrated in specific regions of the OsHV-1 genome, single nucleotide editing is more dispersed along the OsHV-1 transcripts. In conclusion, we reveal the existence of a conserved pan-Herpesvirales transcriptomic architecture of the capsid maturation module and uncover a transcription-based viral counter defence mechanism, which presumably facilitates the evasion of the host ADAR antiviral system.

A Comprehensive Review of the Potential Role of Human Cytomegalovirus (HCMV) Infections in Carcinogenesis

: The herpesvirus family includes Human Cytomegalovirus (HCMV), a potent pathogen capable of infecting humans. In healthy individuals, this infection often presents without specific symptoms. After the initial infection, the virus remains dormant in the body but can reactivate later. Reactivation of the virus is one of the primary causes of illnesses associated with HCMV. Human Cytomegalovirus infection is lifelong, and the virus cannot be eliminated from the human body. Although host cells mount an immune response following infection, HCMV expresses genes that encode products capable of countering and adapting to this immune response. The virus is commonly transmitted through bodily fluids. In immunocompromised individuals, HCMV infection can be extremely dangerous and may result in severe, potentially life-threatening infections. For decades, researchers have been investigating the potential link between HCMV and cancer. Recent studies have shown that HCMV DNA and virus-specific antibodies are present in many types of cancer, suggesting that HCMV may play a significant role in cancer development. Further research on HCMV infection and its role in carcinogenesis will enhance our understanding of this virus and facilitate the development of more effective prevention and treatment strategies. In the following study, we will explore the relationship between HCMV infection and its potential role in cancer development.

Structural definition of pseudorabies virus dUTPase reveals a novel folding dimer in the herpesvirus family

The pseudorabies virus (PRV) causes severe and fatal acute respiratory disease in pigs. During PRV proliferation, the enzyme deoxyuridine 5′-triphosphate nucleotide hydrolase (dUTPase) plays a pivotal role in maintaining a low dUTP/dTTP ratio, thereby ensuring the accuracy of viral DNA replication. However, its structure and catalytic mechanisms have not been fully elucidated. Here, we report the crystal structure of PRV dUTPase at a 2.24 Å resolution and demonstrate an unprecedented dimeric architecture, with a conserved enzyme activity center of the herpesvirus family. The enzyme activity center is located in a cavity between the two domains, forming a pocket for binding substrate dUMP and magnesium ions. Remarkably, the exquisite interface of the dimer is primarily composed of four antiparallel β-sheets, which form 11 hydrogen bonds between the residues P33-V36 and R242-A248 to maintain protein stability. To the best of our knowledge, this is the first report demonstrating that dUTPase exists as a dimer in the herpesvirus family. These findings not only present a novel fold dimeric structure but also deepen the scope of our comprehension of structural diversity in dUTPase family.

Perinatal HIV infection and opportunistic infectious pathology: morphological features of the placenta

Opportunistic infections account for more than 90% of all deaths associated with immunosuppression resulting from exposure to the human immunodeficiency virus (HIV). Fatal opportunistic infections include Pneumocystis pneumonia, cryptococcosis, cytomegalovirus infection, and viral hepatitis B and/or C. HIV-infected pregnant women have a high incidence of cytomegalovirus infection, which increases the risk of transplacental transmission of HIV from mother to fetus. In addition, an important factor in perinatal transmission of HIV is a genital infection caused by herpes simplex virus type 2 detected during pregnancy in HIV-infected women. Also, at present, there is no doubt about the possibility of damage to placental cells by the SARS-CoV-2 virus and its transplacental transmission.The aim of this study was to study the morphological features of the placenta in the presence of opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV2 in HIV-infected pregnant women.Materials and methods. A study was conducted of 21 placentas with various pregnancy outcomes in HIV-infected women, including 12 placentas obtained as a result of term birth, 1 placenta from premature birth at 29 weeks, and 8 observations of failed miscarriages (non-developing pregnancy).Results and discussion. Viral lesions were represented by the action of HIV with giant cell metamorphosis of trophoblast cells and placental macrophages, as well as infiltration by immunocompetent cells and fibrosis of the villous stroma. In addition, groups of immature villi were identified, the edematous stroma of which contained an increased number of large cells with light nuclei. In HIV-infected pregnant women with immunosuppression, the outcome of pregnancy in 8 cases was a miscarriage with a morphologically detected and immunohistochemically confirmed infection caused by herpes simplex virus types 1/2 (3 observations), cytomegalovirus (2 observations), and SARS-CoV-2 (3 observations), in 1 case the outcome of pregnancy was premature birth with morphologically identified and immunohistochemically confirmed infection caused by the Epstein-Barr virus.Conclusion. The placentas of HIV-infected pregnant women are characterized by impaired villous maturation with stromal fibrosis, which is the morphological substrate of chronic placental insufficiency with varying degrees of compensation. If HIVinfected pregnant women have opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV-2, pronounced involutive-dystrophic changes are observed in the placentas — perivillous deposition fibrinoid, petrification, which increases the likelihood of an unfavorable pregnancy outcome in the form of miscarriage or premature birth.

Structure-optimized iridium complex coordination-functionalized ZIF-8-based nanoemitters with HEPES as novel efficient and eco-friendly ECL system for multiplex assays of HSV and VZV

Both herpes simplex virus (HSV) and varicella-zoster virus (VZV) belong to herpesviruses family, and the cutaneous infections with HSV or VZV often present similar clinical symptoms, making it challenging in differentiation. Hence, simultaneous detection of herpes simplex virus (HSV) and varicella-zoster virus (VZV) holds great significance for protecting the public health safety. Herein, simultaneous detection of HSV and VZV was innovatively realized based on electrochemiluminescence (ECL) biosensor. Structure-optimized iridium(III) complex coordinated in ZIF-8 nanoemitters (Irbt-ZIF-8-NH2) were synthesized as anodic emitters. Notably, Irbt-ZIF-8-NH2 showed remarkable ECL performance with N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) as the novel efficient co-reactant over the traditional TPrA. The proposed biosensor in this work demonstrated outstanding performance within the linear range of 10 fM to 1 nM, with the detection limit of 1.5 fM for HSV and 2.2 fM for VZV. Importantly, it also exhibited satisfactory recoveries with RSDs in the analysis of viral nucleic acids samples extracted from HSV or VZV infected cells. This work inevitably provides a promising alternative assay for simultaneously detecting HSV and VZV, which would promote to the advancement of efficient and sensitive techniques to tackle significant global health concerns caused by herpesviruses outbreak in the future.

Ramsay Hunt Syndrome: A Rare Disease of Multiple Cranial Nerve Involvement

Ramsay Hunt Syndrome (RHS) also known as herpes zoster oticus is a viral disease, a member of the human herpes virus family, is a late complication of varicella-zoster virus infection that results in inflammation of the geniculate ganglion of cranial nerve VII. Ramsay Hunt is a clinical diagnosis. The hallmark of the condition is multiple unilateral erythematous vesicles, which are distributed over the auricle and preceded by severe otalgia. If these symptoms are associated with facial nerve palsy, the condition is called RHS which is usually accompanied by vestibulocochlear abnormalities. Diagnosis is often missed or delayed, which can lead to an increased incidence of long-term complications. The condition is self-limiting, but treatment is targeted at decreasing the total duration of the illness as well as providing analgesia and preventing the complications that can occur. This activity reviews the role of the inter professional team in the diagnosis and treatment of RHS. Mugda Med Coll J. 2024; 7(1): 48-52

Assessing the Efficacy of Three Hatchery Disinfectants for the Inactivation of a Lake Sturgeon Herpesvirus (Family: Alloherpesviridae).

Infectious diseases are a leading cause of losses in the aquaculture industry and conservation programs globally. Simultaneously, infectious diseases pose a substantial risk to fish being hatchery-reared and released into natural habitats for conservation purposes, including the Great Lakes lake sturgeon (Acipenser fulvescens, i.e., GL-LST). Recently, an alloherpesvirus (lake sturgeon herpesvirus 2, i.e., LSHV-2) capable of inducing disease and/or mortality in adult and juvenile GL-LSTs was detected in two adult GL-LST populations. To begin developing disease prevention and/or control methods, in vitro experiments were designed to determine the susceptibility of LSHV-2 to disinfectants commonly used in hatchery and aquaculture facilities (Virkon®-Aquatic: potassium peroxymonosulfate; Ovadine®: polyvinylpyrrolidone iodine complex; and Perox-Aid®: hydrogen peroxide). Cultured LSHV-2 was exposed to each disinfectant at two concentrations (Virkon®-Aquatic: 0.5% and 1%; Ovadine®: 50 and 100 ppm; and Perox-Aid®: 500 and 1000 ppm) in duplicate for durations of 1, 10, and 30 min. Following exposure, the disinfectant was neutralized, and after a 14-day incubation period on a white sturgeon × lake sturgeon hybrid cell line (WSxLS), percent reduction was calculated by comparing the 50% tissue culture infectious doses (TCID50/mL) of the virus with and without disinfectant exposure. When exposed to Perox-Aid®, LSHV-2 percent reduction ranged from 58.7% to 99.5%. When exposed to Ovadine®, the percent reduction ranged from 99.4% to 100%. Lastly, the percent reduction when exposed to Virkon®-Aquatic was 100% for both concentrations and all timepoints. The results herein provide evidence that both Virkon®-Aquatic and Ovadine® are virucidal to LSHV-2 and may represent a means to reduce virus transmission risk under field settings.

Detecting drug-resistant human cytomegalovirus mutations in liver transplant recipients: A study of the UL97 gene

Human cytomegalovirus (HCMV or HHV-5) is a member of the beta herpesvirus family and remains dormant for life after the initial infection. However, if conditions such as immunosuppression occur, the virus can become active again and lead to severe diseases. The incidence of disease in solid organ transplant (SOT) recipients is reduced by prophylactic use of ganciclovir (either intravenously or orally). This study aimed to determine the pattern of clinical mutations associated with the cytomegalovirus UL97 gene after treatment with ganciclovir and the effect of these mutations on disease progression in liver transplant recipients infected with Iranian HCMV strains. Six HCMV-positive liver transplant recipients were enrolled, comprising 3 (50.0 %) males and 3 (50.0 %) females. Sequence analysis and mutation detection were performed using Finch software (version 1.4.0) and the NCBI Nucleotide Blast database, whereas phylogenetic analysis was performed using MEGA X (version 10.0.5). Mann-Whitney U nonparametric test, Chi-square test, Spearman's correlation coefficient analysis, were employed for statistical analysis. The results of the study showed that two samples from two patients had mutations in the UL97 gene, and the viral load of the mutated samples decreased after administering antiviral medications. Furthermore, the phylogenetic tree demonstrated a close relationship between the Iranian HCMV strains and global reference sequences.

Macrophage Activation Syndrome in Viral Sepsis.

Macrophage activation syndrome (MAS) is a life-threatening systemic hyperinflammatory syndrome triggered by various infections, particularly viral infections, autoimmune disorders, and malignancy. The condition is characterized by an increased production of proinflammatory cytokines resulting in a cytokine storm and has been associated with poor clinical outcomes. During the COVID-19 pandemic, patients with severe manifestations developed features similar to those of MAS, although these characteristics remained well defined within the lung. Additionally, other viral infections including EBV, the herpes family of viruses, hepatitis viruses, influenza, HIV, and hemorrhagic fevers can be complicated by MAS. The diagnosis and management of the condition remain challenging due to the lack of consensus on specific guidelines, especially among the adult population. Currently, therapeutic options primarily rely on medications that are typically used to treat primary hemophagocytic lymphohistiocytosis, such as corticosteroids and etoposide. In addition, cytokine-targeted therapies present promising treatment options. The objective of this review is to discuss the emergence of MAS in the context of viral infections including, but not limited to, its occurrence in COVID-19.

Serological Evidence of Epstein-Barr Virus Capsid Antigen (EB-CA) Among Pregnant Women from Cottage Hospital, Ilorin

Study’s Excerpt/Novelty This study reveals a significant Epstein-Barr Virus (EBV) prevalence among pregnant women attending Cottage Hospital in Ilorin, with 95.69% of participants testing positive for anti-EBV IgG antibodies. Notably, the highest prevalence was observed among younger women, those in the first trimester, individuals from polygamous families, and those with lower educational levels. These findings underscore the need for increased community awareness and improved personal hygiene practices to reduce EBV infection rates and associated congenital defects. Full Abstract Epstein-Barr Virus (EBV), a member of the Herpesvirus family, has been observed to be increasing among pregnant women, leading to congenital defects. This study aimed to determine the prevalence of EBV infection among pregnant women attending Cottage Hospital in Ilorin. A total of 45 pregnant women were tested, and questionnaires were administered to volunteer subjects after obtaining their informed consent. Approximately 5 ml of blood was aseptically collected via venous puncture from the antecubital fossa and dispensed into EDTA containers. Plasma was separated after centrifugation of the blood, and the obtained plasma was screened for anti-EBV IgG antibodies using ELISA techniques. Results revealed that 43 subjects (95.69%) tested positive for EBV, while 2 (4.4%) tested negative. Among different age groups, women aged 19-20, 26-30, and 36-40 showed a prevalence rate of 100%, with the lowest prevalence of 88.8% recorded among the 31-35 age group. Regarding the pregnancy stage, 100% was seen among first-trimester participants, while the lowest prevalence of 92.3% was noted during the third trimester. The majority of respondents were married, with those from polygamous families and single individuals showing a prevalence of 100%. Participants with primary and secondary education levels displayed the highest prevalence, while those with tertiary education had the lowest. Muslims had the highest prevalence, whereas Christians had the lowest. Moreover, regarding occupation, the unemployed, artisans, and students had the highest prevalence, while civil servants and businesswomen had the lowest prevalence. In conclusion, the results from this study highlight a notable prevalence of EBV (IgG) antibodies among pregnant women. These outcomes emphasize the necessity of raising awareness in the community about the implications of EBV infection and the Significance of maintaining proper personal hygiene to mitigate the chances of infection and spread

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.

Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

In plants and mammals, non-homologous end-joining is the dominant pathway to repair DNA double-strand breaks, making it challenging to generate knock-in events. In this study, we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana benthamiana. We achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation systems. In Arabidopsis thaliana, fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of transformants. In addition, we demonstrated stable and heritable knock-ins in wheat in 1% of the primary transformants. Taken together, our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

Mutagenesis and functional analysis of the varicella-zoster virus portal protein.

Herpesviruses replicate by cleaving concatemeric dsDNA into single genomic units that are packaged through an oligomeric portal present in preformed procapsids. In contrast to what is known about phage portal proteins, details concerning herpesvirus portal structure and function are not as well understood. A panel of 65 Varicella-Zoster virus (VZV) recombinant portal proteins with five amino acid in-frame insertions were generated by random transposon mutagenesis of the VZV portal gene, ORF54. Subsequently, 65 VZVLUC recombinant viruses (TNs) were generated via recombineering. Insertions were mapped to predicted portal domains (clip, wing, stem, wall, crown, and β-hairpin tunnel-loop) and recombinant viruses were characterized for plaque morphology, replication kinetics, pORF54 expression, and classified based on replication in non-complementing (ARPE19) or complementing (ARPE54C50) cell lines. The N- and C-termini were tolerant to insertion mutagenesis, as were certain clip sub-domains. The majority of mutants mapping to the wing, wall, β-hairpin tunnel loop, and stem domains were lethal. Elimination of the predicted ORF54 start codon revealed that the first 40 amino acids of the N-terminus were not required for viral replication. Stop codon insertions in the C-terminus showed that the last 100 amino acids were not required for viral replication. Lastly, a putative protease cleavage site was identified in the C-terminus of pORF54. Cleavage was likely orchestrated by a viral protease; however, processing was not required for DNA encapsidation and viral replication. The panel of recombinants should prove valuable in future studies to dissect mammalian portal structure and function.IMPORTANCEThough nucleoside analogs and a live-attenuated vaccine are currently available to treat some human herpesvirus family members, alternate methods of combating herpesvirus infection could include blocking viral replication at the DNA encapsidation stage. The approval of Letermovir provided proof of concept regarding the use of encapsidation inhibitors to treat herpesvirus infections in the clinic. We propose that small-molecule compounds could be employed to interrupt portal oligomerization, assembly into the capsid vertex, or affect portal function/dynamics. Targeting portal at any of these steps would result in disruption of viral DNA packaging and a decrease or absence of mature infectious herpesvirus particles. The oligomeric portals of herpesviruses are structurally conserved, and therefore, it may be possible to find a single compound capable of targeting portals from one or more of the herpesvirus subfamilies. Drug candidates from such a series would be effective against viruses resistant to the currently available antivirals.

The role of intestinal microbiota in the development of dysfunction of the biliary system in children

Objective: to study the state of the intestinal and biliary microbiota in children with intestinal and gallbladder dysfunction and to determine the features of the component composition of the biliary microbiota. Methods: We examined 20 children with irritable bowel syndrome (IBS). The presence of small intestinal bacterial overgrowth (SIBO) syndrome was determined (using a hydrogen breath test with lactulose), microbial markers of the intestinal and biliary microbiota (using gas chromatography-mass spectrometry). We also performed microscopy of bile (phase-contrast light microscopy) obtained through duodenal intubation. Results: In all children with IBS, SIBO was verified in the small intestine, with insufficiency of the ileocecal valve in half of them, associated with hypomotor dyskinesia of the gallbladder. Microscopy of the bile revealed a large number of crystals and leukocytes. A study of microbial markers of intestinal and biliary microbiota in all children with IBS and SIBO revealed excessive bacterial associative growth of gram-negative opportunistic bacteria in combination with viruses of the Herpes family. An increase in the level of lipopolysaccharides (2 times higher than normal) and a deficiency of microbial markers of the main groups of microorganisms (anaerobic bacteria) responsible for metabolization processes in the enterohepatic circulation (plasmalogen less than 50 μg/ml) were recorded. Excessive growth of 28 species of opportunistic bacteria was detected in bile in diagnostically significant concentrations associated with hypomotor dysfunction of the gallbladder and lithogenicity of bile. Conclusion: A violation of the biliary microbiota was established with an increase in the proportion of gram-negative opportunistic bacteria, the spectrum of which was close to that of the intestine and their association with intestinal and biliary dyskinesia

Anti-CMV IgG Seropositivity is Associated with Plasma Biomarker Evidence of Amyloid-β Accumulation.

Some human studies have identified infection with cytomegalovirus (CMV), a member of the alpha herpesvirus family, as a risk factor for Alzheimer's disease and related dementias (ADRD). To our knowledge, no studies have evaluated associations of CMV seropositivity with plasma biomarkers of ADRD risk in middle-aged adults. In participants recruited for an exercise study, we evaluated cross-sectional associations of CMV seropositivity with: Aβ42/Aβ40 ratio, a low ratio suggestive of central nervous system Aβ accumulation; glial fibrillary acidic protein (GFAP), a measure of neuroinflammation; and neurofilament light (NfL), a measure of neurodegeneration. Anti-CMV IgG was quantified by ELISA. Plasma ADRD biomarkers were quantified using the ultrasensitive SIMOA assay. We used linear regression to evaluate associations of CMV seropositivity with the ADRD biomarkers, adjusting for age, sex, and race (n = 303; Age = 55.7±9.2 years). For ADRD biomarkers significantly associated with CMV seropositivity, we evaluated continuous associations of anti-CMV IgG levels with the ADRD biomarkers, excluding CMV seronegative participants. 53% of participants were CMV seropositive. CMV seropositivity was associated with a lesser Aβ42/Aβ40 ratio (β=-3.02e-03 95% CI [-5.97e-03, -7.18e-05]; p = 0.045). In CMV seropositive participants, greater anti-CMV IgG levels were associated with a lesser Aβ42/Aβ40 ratio (β=-4.85e-05 95% CI[-8.45e-05, -1.25e-05]; p = 0.009). CMV seropositivity was not associated with plasma GFAP or NfL in adjusted analyses. CMV seropositivity was associated with a lesser plasma Aβ42/Aβ40 ratio. This association may be direct and causally related to CMV neuro-cytotoxicity or may be indirect and mediated by inflammatory factors resulting from CMV infection burden and/or the immune response.

Raman spectroscopy of lymphocytes from patients with the Epstein–Barr virus infection

In this study, Raman spectroscopy is applied to trace lymphocytes activation following contact with the Epstein–Barr virus (EBV) of the herpesvirus family. The biomarker of cell activation is found to be the 520 cm−1 band, indicating formation of immunoglobulins. The blood samples are obtained from patients diagnosed with infectious mononucleosis and treated at the University Hospital in Kraków. The lymphocytes’ Raman spectra are collected using a mapping technique, exciting samples with a 514.5 nm line of Ar + laser. Measurements are performed on the 1st, 4th, 6th, 12th and 30th day of hospitalization, until the patient has recovered. The highest intensity of the immunoglobulin marker is observed on the 4th day of hospitalization, while the results of the blood count of patients show the greatest increase in the number of lymphocytes at the beginning of hospitalization. No activated lymphocytes were observed in the blood of healthy volunteers. Some information is provided by the evaluation of B-cell activation by estimating the activated areas in the cells, which are determined by the presence of the Ig marker. The 900 cm−1 band and band around 1450 cm−1 are also analyzed as markers of the presence of the latent membrane protein, LMP2A (and 2B), of the EBV viral protein. The anomalous degree of depolarization observed in B-cells in the course of EBV infection appears to be due to the influence of a virus protein, disrupting BCR signal transduction.

Resorbable nanofibrous membranes for local and sustained co-delivery of acyclovir and ketorolac in herpes therapy

Herpes simplex and herpes zoster are both viral infections caused by members of the herpesvirus family. The former is characterized by painful, fluid-filled blisters or sores on the skin and mucous membranes, while the latter presents as a painful rash with blisters, typically occurring in a single band or patch along one side of the body. The treatment remains a challenge since current antiviral therapy via oral administration may lead to unfavorable side effects such as headaches, nausea, and diarrhea. This study used electrospinning to develop biodegradable nanofibrous poly(lactic-co-glycolic acid) (PLGA) membranes for delivery of both acyclovir and ketorolac. The structure of the spun nanofibers was assessed via scanning electron microscopy (SEM), and the appearance of loaded acyclovir and ketorolac in the nanofibers was confirmed with Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Release profiles of these drugs from the nanofibrous membranes were assessed using in vitro elution studies, high-performance liquid chromatography (HPLC) assays, and in vivo drug release patterns. The electrospun nanofibers had a size range of 283–725 nm in diameter, resembling the extracellular matrix of natural tissue and demonstrated excellent flexibility and extensibility. Notably, the drug-eluting nanofibers exhibited an extended release of high levels of acyclovir and ketorolac over a 21-day period. Thus, biodegradable drug-eluting membranes with a prolonged drug release could be a potential therapeutic approach for treating herpes infections.