Virus Infection Research Articles

Associations of insulin sensitivity and immune inflammatory responses with child blood lead (Pb) and PM2.5 exposure at an e-waste recycling area during the COVID-19 lockdown.

Fine particular matter (PM2.5) and lead (Pb) exposure can induce insulin resistance, elevating the likelihood of diabetes onset. Nonetheless, the underlying mechanism remains ambiguous. Consequently, we assessed the association of PM2.5 and Pb exposure with insulin resistance and inflammation biomarkers in children. A total of 235 children aged 3-7years in a kindergarten in e-waste recycling areas were enrolled before and during the Corona Virus Disease 2019 (COVID-19) lockdown. Daily PM2.5 data was collected and used to calculate the individual PM2.5 daily exposure dose (DED-PM2.5). Concentrations of whole blood Pb, fasting blood glucose, serum insulin, and high mobility group box 1 (HMGB1) in serum were measured. Compared with that before COVID-19, the COVID-19 lockdown group had lower DED-PM2.5 and blood Pb, higher serum HMGB1, and lower blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR) index. Decreased DED-PM2.5 and blood Pb levels were linked to decreased levels of fasting blood glucose and increased serum HMGB1 in all children. Increased serum HMGB1 levels were linked to reduced levels of blood glucose and HOMA-IR. Due to the implementation of COVID-19 prevention and control measures, e-waste dismantling activities and exposure levels of PM2.5 and Pb declined, which probably reduced the association of PM2.5 and Pb on insulin sensitivity and diabetes risk, but a high level of risk of chronic low-grade inflammation remained. Our findings add new evidence for the associations among PM2.5 and Pb exposure, systemic inflammation and insulin resistance, which could be a possible explanation for diabetes related to environmental exposure.

“If I die for touching him, let me die”: a rapid ethnographic assessment of cultural practices and Ebola transmission in high-risk border regions of Tanzania

BackgroundEbola Virus Disease (EVD) is a rare but contagious disease caused by Ebola Virus (EBOV). The first Ebola outbreaks were reported in the Democratic Republic of Congo (DRC) before subsequent reported cases in Western and East African countries, including Uganda, which borders Tanzania. Proximity to EVD-infected countries raises the prospect of cross-border transmission, raising alarm in Tanzania. This study aimed to explore the cultural practices likely to prevent or escalate EVD transmission in the event of its outbreak in the country.MethodsThis rapid ethnographic assessment employed observation, interviews, and focus group discussions to collect data from people with diverse characteristics in five regions of Tanzania Mainland namely, Kagera, Kigoma, Mwanza and Songwe regions and Zanzibar Island. The qualitative data was then subjected to thematic analysis.FindingsCultural practices may escalate the transmission of EVD and hinder its prevention and control. These cultural practices include caring sick people at home, confirmation of death, mourning, and body preparation for burial. Communal life, ceremonies, and social gatherings were other aspects observed to have the potential for compounding EVD transmission and hindering its containment in case of an outbreak.ConclusionCultural practices may escalate EVD transmission as identified in the study settings. As such, Risk Communication and Community Engagement (RCCE) activities should be interventionist in transforming cultural practices that may escalate the spread of EVD as part of preparedness, prevention, and control efforts in the event of an outbreak.

Translation Inhibition Mediated by Interferon-Stimulated Genes during Viral Infections

Viruses often pose a significant threat to the host through the exploitation of cellular machineries for their own benefit. In the context of immune responses, myriad host factors are deployed to target viral RNAs and inhibit viral protein translation, ultimately hampering viral replication. Understanding how “non-self” RNAs interact with the host translation machinery and trigger immune responses would help in the development of treatment strategies for viral infections. In this review, we explore how interferon-stimulated gene products interact with viral RNA and the translation machinery in order to induce either global or targeted translation inhibition.

A Review of the Bromodomain and Extraterminal Domain Epigenetic Reader Proteins: Function on Virus Infection and Cancer

The BET (bromodomain and extraterminal domain) family of proteins, particularly BRD4 (bromodomain-containing protein 4), plays a crucial role in transcription regulation and epigenetic mechanisms, impacting key cellular processes such as proliferation, differentiation, and the DNA damage response. BRD4, the most studied member of this family, binds to acetylated lysines on both histones and non-histone proteins, thereby regulating gene expression and influencing diverse cellular functions such as the cell cycle, tumorigenesis, and immune responses to viral infections. Given BRD4’s involvement in these fundamental processes, it is implicated in various diseases, including cancer and inflammation, making it a promising target for therapeutic development. This review comprehensively explores the roles of the BET family in gene transcription, DNA damage response, and viral infection, discussing the potential of targeted small-molecule compounds and highlighting BET proteins as promising candidates for anticancer therapy.

COVID-19 in children: Clinical presentation and hospital course at a district hospital in South Africa

Limited data exist on South African children hospitalised with COVID-19 in district hospitals. We describe the presentation and outcomes of children admitted to a level 1 and 2 hospital and compare this with children admitted to a level 2 and 3 hospital.Contribution: This study highlights that young age is an important risk factor for hospitalisation with severe COVID-19. Infants with HIV exposure and prematurity are disproportionately represented among admissions. Furthermore, we notice a high number of children with current or new tuberculosis confirming the interplay between viral infections and childhood tuberculosis.

Investigation of Factors Affecting the Prevalence of Sinusitis in Children Referred to Abu Ali Sina Balkhi Educational Hospital

Sinusitis is one of the most common medical problems in children, caused by inflammation and infection in the nasal sinuses. This disease can have a significant impact on the growth and health of children. Investigating the factors affecting the prevalence of sinusitis in children is necessary in order to take appropriate preventive and therapeutic measures. In this regard, the present study aimed to investigate the factors affecting the prevalence of sinusitis among children referred to Abu Ali Sina Educational Hospital in Balkhi. Materials and Methods: This study includes the design of a prospective descriptive study, data were collected using patients' files, then by analyzing the data, the causes of the prevalence of sinusitis in children referred to Abu Ali Sina Balkhi Educational Hospital will be identified and the results will be presented in the form of a scientific article. The findings showed that the prevalence of sinusitis was higher among children admitted to Abu Ali Sina Educational Hospital in Balkhi and viral infections (influenza 20%, adenovirus 24% and Ronovirus 40%) were reported. The majority of patients had symptoms such as nasal congestion and discharge, a feeling of congestion in the ears, headache, and fever. In the majority of patients, their growth and development disorders have also been observed.

CD39 Is Expressed on Functional Effector and Tissue-resident Memory CD8+ T Cells.

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on Ag-specific CD8+ short-lived effector cells, while it's co-ectoenzyme, CD73, is found on memory precursor effector cells (MPECs) invivo. Inhibition of CD39 enzymatic activity during invitro T cell priming enhances MPEC differentiation invivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory T cell (TRM cell) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine TRM cells across several nonlymphoid tissues and melanoma, whereas CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ TRM cells are fully functional when stimulated ex vivo with cognate Ag, further expanding the identity of CD39 beyond a T cell exhaustion marker.

Incidence and Characteristics of Pediatric Patients with Acute Otitis Hospitalized in a Romanian Infectious Diseases Hospital

Background: Otic involvement is common in children during acute infectious diseases, and is an important cause of morbidity and health service utilization. Methods: We performed a retrospective analysis of pediatric cases hospitalized in the largest infectious disease hospital in Romania between 2018 and 2023, with the aim of quantifying the incidence and impact of acute otitis (AO) according to pediatric age subgroups. Results: A total of 1118 cases diagnosed with AO were eligible and included in the analysis. Acute congestive otitis media was the most common subtype, identified in 53.3% of cases, followed by acute purulent otitis media (APOM) in 26.7% of children. The majority of AO cases (69.9%) were diagnosed in the pre-pandemic period (2018–2019), and infants (10.6%), toddlers (49.4%), and preschoolers (29.2%) were the most affected age groups. A viral infection associated with the AO episode was documented in 49.6% of cases. Influenza viruses were most commonly reported (20.5%), followed by SARS-CoV-2 (5.8%), and adenovirus (4.9%). A total of 38 cases of AO were identified in children with measles. In 15.9% of APOM cases, Streptococcus pneumoniae was isolated by culture from otic secretions. The duration of hospitalization was longer in children with APOM and acute otitis externa compared to the other subtypes of AO (p < 0.001). Conclusions: Our study highlights the importance of ENT (ear, nose, and throat) monitoring in children hospitalized for acute infectious diseases, as the majority of AO cases occur in the context of a viral infection. These findings emphasize the necessity for tailored assessment and intervention in suspected cases of AO, especially in young children under 5 years of age.

Neutrophilia in the bronchoalveolar lavage fluid increases coughing during flexible fiberoptic bronchoscopy in a pediatric cohort

ObjectiveThis study is an addition to the already published prospective randomized double-blinded trial by Tschiedel et al. that compared two different sedation regimes in fiberoptic flexible bronchoscopy in pediatric subjects. The objective of the presented study is to analyze the correlation between the neutrophil percentage of the bronchoalveolar lavage fluid (BALF) and coughing episodes during bronchoscopy.MethodsFifty subjects, aged 1–17 years, received flexible fiberoptic bronchoscopy under deep sedation. The BALF of 39 subjects was analyzed with reference to cytology and microbiology.ResultsThe percentage of neutrophils from the total cell count ranged from 0% to 95.3% (median 2.7). Nineteen patients (49%) had a percentage of ≥3.0%. Pearson's correlation showed a high correlation (r = 0.529, p = 0.001) between the coughing episodes per minute and the neutrophil percentage in the BALF. Analysis of variance showed a significant difference in neutrophil percentage between the indication groups (p = 0.013). The t-test (p = 0.019) showed a significant difference between the neutrophil percentage for patients with a probable airway infection under immunosuppression (median 2.9) and patients with cystic fibrosis (median 49.6). The linear regression analysis showed a significantly stronger impact of the neutrophil percentage on coughing frequency than the sedation regime (βneutrophils = 0.526 with p = 0.001 vs. βsedation = 0.165 with p = 0.251).ConclusionWhen bronchoscopy is to be performed on a pediatric patient with suspected bacterial or viral infection, and therefore neutrophilic airway inflammation, coughing is to be expected.

RAbDesFlow: A novel workflow for computational recombinant antibody design for healthcare engineering

Abstract Background Recombinant antibodies have emerged as a promising solution to tackle antigen specificity, enhancement of immunogenic potential and versatile functionalization to treat human diseases. The development of single chain variable fragments (scFv) has helped accelerate treatment in cancers and viral infections, due to their favorable pharmacokinetics and human compatibility. However, designing recombinant antibodies is traditionally viewed as a genetic engineering problem, with phage display and cell free systems playing a major role in sequence selection for gene synthesis. The process of antibody engineering involves complex and time-consuming laboratory techniques, which demand substantial resources and expertise. The success rate of obtaining desired antibody candidates through experimental approaches can be modest, necessitating iterative cycles of selection and optimization. With ongoing advancements in technology, in silico design of diverse antibody libraries, screening and identification of potential candidates for in vitro validation can be accelerated. Methods To meet this need, we have developed rAbDesFlow, a unified computational workflow for recombinant antibody engineering with open-source programs and tools for ease of implementation. Results The workflow encompasses five computational modules to perform antigen selection, antibody library generation, antigen and antibody structure modeling, antigen-antibody interaction modeling, structure analysis, and consensus ranking of potential antibody sequences for synthesis and experimental validation. The proposed workflow has been demonstrated through design of recombinant antibodies for the ovarian cancer antigen Mucin-16 (CA-125). Conclusions This approach can serve as a blueprint for designing similar engineered molecules targeting other biomarkers, allowing for a simplified adaptation to different cancer types or disease-specific antigens.

Multi-Omics Analysis by Machine Learning Identified Lysophosphatidic Acid as a Biomarker and Therapeutic Target for Porcine Reproductive and Respiratory Syndrome.

As a significant infectious disease in livestock, porcine reproductive and respiratory syndrome (PRRS) imposes substantial economic losses on the swine industry. Identification of diagnostic markers and therapeutic targets has been a focal challenge in PPRS prevention and control. By integrating metabolomic and lipidomic serum analyses of clinical pig cohorts through a machine learning approach with in vivo and in vitro infection models, lysophosphatidic acid (LPA) is discovered as a serum metabolic biomarker for PRRS virus (PRRSV) clinical diagnosis. PRRSV promoted LPA synthesis by upregulating the autotaxin expression, which causes innate immunosuppression by dampening the retinoic acid-inducible gene I (RIG-I) and type I interferon responses, leading to enhanced virus replication. Targeting LPA demonstrated protection against virus infection and associated disease outcomes in infected pigs, indicating that LPA is a novel antiviral target against PRRSV. This study lays a foundation for clinical prevention and control of PRRSV infections.

Cardiac effects of direct anti-viral treatment in type II diabetic patients with hepatitis C infection

BackgroundThe link between diabetes mellitus and chronic hepatitis C infection remains well established. It is estimated that up to one third of chronic hepatitis C patients have type II diabetes mellitus. Hepatitis C virus infection is one of the main global health burdens. Sofosbuvir and Daclatasvir are used as effective antiviral inhibitors of hepatitis C virus. The cardiovascular effects of those drugs are not well studied. We used electrocardiography and echocardiography with global longitudinal strain assessment by speckle tracking to detect their effect on cardiac function.Methods and resultsOne hundred diabetic patients with hepatitis C infection were included in the study. Abdominal ultrasound and laboratory work up were carried out for all participants. Left ventricular systolic and diastolic function were assessed by 2D-echocardiography and global longitudinal strain, before and 3 months after treatment. Results showed significant decrease in global longitudinal strain 3 months after therapy (-21 ± 4 vs. -18 ± 7; P < 0.001) but other echocardiographic findings showed no significant changes.ConclusionsSofosbuvir and Daclatasvir were associated with early left ventricular systolic dysfunction as assessed by global longitudinal strain in diabetic patients. More deterioration in left ventricular systolic function was detected among those with Child-Pough class B. Further long-term follow-up may be required.

Viral hepatitis in China during 2002–2021: epidemiology and influence factors through a country-level modeling study

BackgroundViral hepatitis imposes a heavy disease burden worldwide and is also one of the most serious public health problems in China. We aimed to describe the epidemiological characteristics of hepatitis in China and to investigate the influencing factors.MethodsWe first used the JoinPoint model to analyze the percentage change (APC) and average annual percentage change (AAPC) of hepatitis in Chinese provinces from 2002 to 2021. We then explored the influencing factors by using the time-series global principal component analysis (GPCA) and the panel fixed-effects model.ResultsThe disease burden varied across different provinces from 2002 to 2021. The AAPC of the total HAV incidence decreased by 10.39% (95% CI: [-12.70%, -8.02%]) from 2002 to 2021. Yet the AAPC of HBV, HCV, and HEV increased by 1.50% (95% CI: [0.23%, 2.79%]), 13.99% (95% CI: [11.28%, 16.77%]), and 7.10% (95% CI: [0.90%, 13.69%]), respectively. The hotspots of HAV, HBV, HCV, and HEV moved from the west to the center, from the northwest to the southeast, from the northeast to the whole country, and from the northeast to the southeast, respectively. Different types of viral hepatitis infections were associated with hygiene, pollutant, and meteorological factors. Their roles in spatial-temporal incidence were expressed by panel regression functions.ConclusionsViral hepatitis infection in China showed spatiotemporal heterogeneity. Interventions should be tailored to its epidemiological characteristics and determinants of viral hepatitis.

Expected vs Reported Chronic Hepatitis B Infection Cases in Persons with Active Tuberculosis - California, 2016-2020.

Epidemiologic data regarding persons with active tuberculosis (TB) and chronic hepatitis B virus (cHBV) infection are limited because of lack of routine surveillance of cHBV in persons with TB. Potential underdiagnosis of cHBV in California among those with TB is concerning. We matched TB and cHBV registries to identify cHBV infections among persons diagnosed with TB during 2016-2020 and described their demographic characteristics. We calculated expected cHBV cases among persons with TB for each demographic characteristic using published cHBV prevalence estimates for the locations of birth for persons with TB. Estimates were from general or emigrant adult and teen populations. Reported cHBV infection among persons with TB were 23% lower than expected, particularly among Asian persons, persons living in the two healthiest Healthy Places Index quartiles, and residents of less populated jurisdictions in California. Results show the possibility exists for underdiagnosis of cHBV in persons with TB in California.

Neural Network Enables High Accuracy for Hepatitis B Surface Antigen Detection with a Plasmonic Platform.

The detection of hepatitis B surface antigen (HBsAg) is critical in diagnosing hepatitis B virus (HBV) infection. However, existing clinical detection technologies inevitably cause certain inaccuracies, leading to delayed or unwarranted treatment. Here, we introduce a label-free plasmonic biosensing method based on the thickness-sensitive plasmonic coupling, combined with supervised deep learning (DL) using neural networks. The strategy of utilizing neural networks to process output data can reduce the limit of detection (LOD) of the sensor and significantly improve the accuracy (from 93.1%-97.4% to 99%-99.6%). Compared with widely used emerging clinical technologies, our platform achieves accurate decisions with higher sensitivity in a short assay time (∼30 min). The integration of DL models considerably simplifies the readout procedure, resulting in a substantial decrease in processing time. Our findings offer a promising avenue for developing high-precision molecular detection tools for point-of-care (POC) applications.

Sample-to-Answer Detection of SARS-CoV-2 Viremia Using Thermally Responsive Alkane Partitions.

The diagnosis of bloodborne viral infections (viremia) is currently relegated to central laboratories because of the complex procedures required to detect viruses in blood samples. The development of point-of-care diagnostics for viremia would enable patients to receive a diagnosis and begin treatment immediately instead of waiting days for results. Point-of-care systems for viremia have been limited by the challenges of integrating multiple precise steps into a fully automated (i.e., sample-to-answer), compact, low-cost system. We recently reported the development of thermally responsive alkane partitions (TRAPs), which enable the complete automation of diagnostic assays with complex samples. Here we report the use of TRAPs for the sample-to-answer detection of viruses in blood using a low-cost portable device and easily manufacturable cassettes. Specifically, we demonstrate the detection of SARS-CoV-2 in spiked blood samples, and we show that our system detects viremia in COVID-19 patient samples with good agreement to conventional RT-qPCR. We anticipate that our sample-to-answer system can be used to rapidly diagnose SARS-CoV-2 viremia at the point of care, leading to better health outcomes for patients with severe COVID-19 disease, and that our system can be applied to the diagnosis of other life-threatening bloodborne viral diseases, including Hepatitis C and HIV.

The antibodies against the A137R protein drive antibody-dependent enhancement of African swine fever virus infection in porcine alveolar macrophages

ABSTRACT African swine fever virus (ASFV) is the causative agent of African swine fever (ASF), a highly contagious disease that can kill up to 100% of domestic pigs and wild boars. It has been shown that the pigs inoculated with some ASF vaccine candidates display more severe clinical signs and die earlier than do pigs not immunized. We hypothesize that antibody-dependent enhancement (ADE) of ASFV infection may be caused by the presence of some unidentified antibodies. In this study, we found that the ASFV-encoded structural protein A137R (pA137R) can be recognized by the anti-ASFV positive sera, indicating that the anti-pA137R antibodies are induced in the ASFV-infected pigs. Interestingly, our results demonstrated that the anti-pA137R antibodies produced in rabbits or pigs enhanced viral replication of different ASFV strains in primary porcine alveolar macrophages (PAMs), the target cells of ASFV. Mechanistic investigations revealed that anti-pA137R antibodies were able to promote the attachment of ASFV to PAMs and two types of Fc gamma receptors (FcγRs), FcγRII and FcγRIII, mediated the ADE of ASFV infection. Taken together, anti-pA137R antibodies are able to drive ASFV ADE in PAMs. These findings shed new light on the roles of anti-ASFV antibodies and have implications for the pathophysiology of the disease and the development of ASF vaccines.

West Nile Virus-Induced Expression of Senescent Gene Lgals3bp Regulates Microglial Phenotype within Cerebral Cortex

Microglia, the resident macrophages of the central nervous system, exhibit altered gene expression in response to various neurological conditions. This study investigates the relationship between West Nile Virus infection and microglial senescence, focusing on the role of LGALS3BP, a protein implicated in both antiviral responses and aging. Using spatial transcriptomics, RNA sequencing and flow cytometry, we characterized changes in microglial gene signatures in adult and aged mice following recovery from WNV encephalitis. Additionally, we analyzed Lgals3bp expression and generated Lgals3bp-deficient mice to assess the impact on neuroinflammation and microglial phenotypes. Our results show that WNV-activated microglia share transcriptional signatures with aged microglia, including upregulation of genes involved in interferon response and inflammation. Lgals3bp was broadly expressed in the CNS and robustly upregulated during WNV infection and aging. Lgals3bp-deficient mice exhibited reduced neuroinflammation, increased homeostatic microglial numbers, and altered T cell populations without differences in virologic control or survival. These data indicate that LGALS3BP has a role in regulating neuroinflammation and microglial activation and suggest that targeting LGALS3BP might provide a potential route for mitigating neuroinflammation-related cognitive decline in aging and post-viral infections.

Uncovering the Interaction between TRAF1 and MAVS in the RIG-I Pathway to Enhance the Upregulation of IRF1/ISG15 during Classical Swine Fever Virus Infection

Classical swine fever (CSF) is caused by the classical swine fever virus (CSFV), which poses a threat to swine production. The activation of host innate immunity through linker proteins such as tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) is crucial for the induction of the NF-κB pathway. Recent research has revealed the involvement of mitochondrial antiviral-signaling protein (MAVS) in the interaction with TRAF2, 3, 5, and 6 to activate both the NF-κB and IRF3 pathways. This study revealed that CSFV infection led to the upregulation of TRAF1 mRNA and protein levels; moreover, TRAF1 overexpression inhibited CSFV replication, while TRAF1 knockdown promoted replication, highlighting its importance in the host response to CSFV infection. Additionally, the expression of RIG-I, MAVS, TRAF1, IRF1, and ISG15 were detected in PK-15 cells infected with CSFV, revealing that TRAF1 plays a role in regulating IRF1 and ISG15 within the RIG-I pathway. Furthermore, Co-IP, GST pull-down, and IFA analyses demonstrated that TRAF1 interacted with MAVS and co-localized in the cytoplasm during CSFV infection. Ultimately, TRAF1 acted as a novel member of the TRAF family, bound to MAVS as a linker molecule, and functioned as a mediator downstream of MAVS in the RIG-I/MAVS pathway against CSFV replication.

Sources of Human Immunodeficiency Virus Infections Among Men Who Have Sex With Men With a Migration Background: A Viral Phylogenetic Case Study in Amsterdam, The Netherlands.

Men and women with a migration background comprise an increasing proportion of incident human immunodeficiency virus (HIV) cases across Western Europe. To characterize sources of transmission in local transmission chains, we used partial HIV consensus sequences with linked demographic and clinical data from the opt-out AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort of people with HIV in the Netherlands and identified phylogenetically and epidemiologically possible HIV transmission pairs in Amsterdam. We interpreted these in the context of estimated infection dates, and quantified population-level sources of transmission to foreign-born and Dutch-born Amsterdam men who have sex with men (MSM) within Amsterdam transmission chains. We estimate that Dutch-born MSM were the predominant sources of infections among all Amsterdam MSM who acquired their infection locally in 2010-2021, and among almost all foreign-born Amsterdam MSM subpopulations. Stratifying by 2-year intervals indicated time trends in transmission dynamics, with a majority of infections originating from foreign-born MSM since 2016, although uncertainty ranges remained wide. Native-born MSM have predominantly driven HIV transmissions in Amsterdam in 2010-2021. However, in the context of rapidly declining incidence in Amsterdam, the contribution from foreign-born MSM living in Amsterdam is increasing, with some evidence that most local transmissions have been from foreign-born Amsterdam MSM since 2016.