Human Virus Infection Research Articles

Pharmacophore modeling and QSAR analysis of anti-HBV flavonols.

Due to its global burden, Targeting Hepatitis B virus (HBV) infection in humans is crucial. Herbal medicine has long been significant, with flavonoids demonstrating promising results. Hence, the present study aimed to establish a way of identifying flavonoids with anti-HBV activities. Flavonoid structures with anti-HBV activities were retrieved. A flavonol-based pharmacophore model was established using LigandScout v4.4. Screening was performed using the PharmIt server. A QSAR equation was developed and validated with independent sets of compounds. The applicability domain (AD) was defined using Euclidean distance calculations for model validation. The best model, consisting of 57 features, was generated. High-throughput screening (HTS) using the flavonol-based model resulted in 509 unique hits. The model's accuracy was further validated using a set of FDA-approved chemicals, demonstrating a sensitivity of 71% and a specificity of 100%. Additionally, the QSAR model with two predictors, x4a and qed, exhibited predictive solid performance with an adjusted-R2 value of 0.85 and 0.90 of Q2. PCA showed essential patterns and relationships within the dataset, with the first two components explaining nearly 98% of the total variance. Current HBV therapies tend to fail to provide a complete cure, emphasizing the need for new therapies. This study's importance was to highlight flavonols as potential anti-HBV medicines, presenting a supplementary option for existing therapy. The QSAR model has been validated with two separate chemical sets, guaranteeing its reproducibility and usefulness for other flavonols by utilizing the predictive characteristics of X4A and qed. These results provide new possibilities for discovering future anti-HBV drugs by integrating modeling and experimental research.

Establishing an immune correlate of protection for Nipah virus in nonhuman primates

The limited but recurrent outbreaks of the zoonotic Nipah virus (NiV) infection in humans, its high fatality rate, and the potential virus transmission from human to human make NiV a concerning threat with pandemic potential. There are no licensed vaccines to prevent infection and disease. A recombinant Hendra virus soluble G glycoprotein vaccine (HeV-sG-V) candidate was recently tested in a Phase I clinical trial. Because NiV outbreaks are sporadic, and with a few cases, licensing will likely require an alternate regulatory licensing pathway. Therefore, determining a reliable vaccine correlate of protection (CoP) will be critical. We assessed the immune responses elicited by HeV-sG-V in African Green monkeys and its relationship with protection from a NiV challenge. Data revealed values of specific binding and neutralizing antibody titers that predicted survival and allowed us to establish a mechanistic CoP for NiV Bangladesh and Malaysia strains.

Discovery of a Small Molecule with an Inhibitory Role for RAB11.

RAB11, a pivotal RabGTPase, regulates essential cellular processes such as endocytic recycling, exocytosis, and autophagy. The protein was implicated in various human diseases, including cancer, neurodegenerative disorders, viral infections, and podocytopathies. However, a small-molecular inhibitor is lacking. The complexity and workload associated with potential assays make conducting large-scale screening for RAB11 challenging. We employed a tiered approach for drug discovery, utilizing deep learning-based computational screening to preselect compounds targeting a specific pocket of RAB11 protein with experimental validation by an in vitro platform reflecting RAB11 activity through the exocytosis of GFP. Further validation included the exposure of Drosophila by drug feeding. In silico pre-screening identified 94 candidates, of which 9 were confirmed using our in vitro platform for Rab11 activity. Focusing on compounds with high potency, we assessed autophagy, which independently requires RAB11, and validated three of these compounds. We further analyzed the dose-response relationship, observing a biphasic, potentially hormetic effect. Two candidate compounds specifically caused a shift in Rab11 vesicles to the cell periphery, without significant impact on Rab5 or Rab7. Drosophila larvae exposed to another candidate compound with predicted oral bioavailability exhibited minimal toxicity, subcellular dispersal of endogenous Rab11, and a decrease in RAB11-dependent nephrocyte function, further supporting an inhibitory role. Taken together, the combination of computational screening and experimental validation allowed the identification of small molecules that modify the function of Rab11. This discovery may further open avenues for treating RAB11-associated disorders.

Herpes simplex virus presenting as an oropharyngeal mass.

Present a clinically challenging case of an immunocompetent 74-year-old male who presented with marked dyspnea and hemoptysis. After the airway was secured, direct laryngoscopy revealed a large, fungating, hemorrhagic mass of the left lateral pharyngeal wall and surrounding structures. Chart review of a single patient. This patient provided consent for his case materials and images to be used for educational purposes and publication. The clinical appearance of the mass was suspicious for an aggressive neoplasm. Initial biopsy of the mass was nonspecific, revealing necrosis and inflammation, but was negative for malignancy. Due to concern for bacterial supraglottitis, empiric treatment with antibiotics was initiated. Cultures were positive for Fusobacterium necrophorum. Repeat biopsy samples showed signs of underlying human simplex virus (HSV) infection, which was confirmed with polymerase chain reaction (PCR) testing. After addition of acyclovir, the patient began to improve clinically and was eventually decannulated. There was complete resolution of the mass at his 1-month follow-up. HSV supraglottitis is a rare, rapidly progressive, and highly morbid condition. Lack of overt patient risk factors, frequently inconclusive biopsies, and clinical appearance mimicking other etiologies make diagnosis challenging. Superimposed bacterial infection is even less common and may contribute to increased disease severity and progression.

CONHECIMENTOS SOBRE RASTREIO E DIAGNÓSTICO PRECOCE DE CÂNCER DE COLO UTERINO ENTRE AS MULHERES QUE FREQUENTAM UM AMBULATÓRIO DE UM CENTRO UNIVERSITÁRIO NA CIDADE DE PORTO VELHO – RO - BRASIL

Cervical cancer (CCU) is one of the most common types among women, making early diagnosis essential for better prognoses. It is characterized by slow progression, but it is amenable to screening and rapid detection, which can lead to effective treatment and a promising prognosis. Human papiloma virus (HPV) infection, especially by subtypes 16 and 18, is a necessary but not sufficient condition for the development of cervical cancer. The oncotic cytology test (Pap smear) aims to detect precursor lesions of CCU. This study investigated the level of knowledge about cervical cancer screening and early diagnosis among women attending an outpatient clinic at a University Center in Porto Velho, RO. A qualitative and descriptive approach was used through questionnaires to assess understanding of the preventive exam (Pap smear), risk factors, and preventive practices. The results showed: (i) high adherence to the cervical cancer preventive exam among participants; (ii) non-use of condoms (70%); (iii) educational actions on the preventive exam (60%); (iv) structural and personal barriers limiting access to the preventive exam; (v) 56.7% of participants had information about HPV; (vi) 83.3% of participants reported knowledge of cervical cancer; (vii) lack of knowledge about the frequency of the preventive exam in 55% of participants; (viii) 88.3% believe that early diagnosis improves prognosis and treatment success. The results of this study may help to develop effective educational interventions that encourage the preventive exam, contributing to reducing incidence and mortality rates associated with CCU, and improving women’s health in the region.

The kinetics of SARS-CoV-2 infection based on a human challenge study

Studying the early events that occur after viral infection in humans is difficult unless one intentionally infects volunteers in a human challenge study. Here, we use data about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in such a study in combination with mathematical modeling to gain insights into the relationship between the amount of virus in the upper respiratory tract and the immune response it generates. We propose a set of dynamic models of increasing complexity to dissect the roles of target cell limitation, innate immunity, and adaptive immunity in determining the observed viral kinetics. We introduce an approach for modeling the effect of humoral immunity that describes a decline in infectious virus after immune activation. We fit our models to viral load and infectious titer data from all the untreated infected participants in the study simultaneously. We found that a power-law with a power h < 1 describes the relationship between infectious virus and viral load. Viral replication at the early stage of infection is rapid, with a doubling time of ~2 h for viral RNA and ~3 h for infectious virus. We estimate that adaptive immunity is initiated ~7 to 10 d postinfection and appears to contribute to a multiphasic viral decline experienced by some participants; the viral rebound experienced by other participants is consistent with a decline in the interferon response. Altogether, we quantified the kinetics of SARS-CoV-2 infection, shedding light on the early dynamics of the virus and the potential role of innate and adaptive immunity in promoting viral decline during infection.

Knowledge of Human Monkeypox Virus Infection among Healthcare Providers and Associated Factors in Addis Ababa, Ethiopia.

Human monkeypox virus infection (mpox) is a reemerging viral zoonotic disease that has been occurring outside of locations where it has been endemic in Africa. To understand the shifting epidemiology of this disease and respond accordingly, increased clinical skill and professional capabilities are essential. However, there are no studies assessing the knowledge of healthcare professionals in Ethiopia on mpox. Hence, this paper aimed to assess knowledge of the infection and associated factors among healthcare providers in Addis Ababa, Ethiopia, specifically knowledge of diagnosis and treatment of mpox, from November 14, 2022 to November 25, 2022. A facility-based cross-sectional study design was used. Knowledge was assessed using a structured questionnaire, and a 70% Bloom's cutoff point was used to classify the scores. A pretest was conducted in a similar setting before data collection. Frequencies, percentages, and bivariate and multivariate logistic regression analyses were used. The majority of participants, 128 (64.6% with 95% CI), scored below 70% on knowledge questions. Professionals with experience of 5 years or less had better knowledge than those who had worked longer (adjusted odds ratio: 0.301; 95% CI: 0.149-0.609; P = 0.000). Knowledge of mpox among healthcare providers in Addis Ababa was poor across sociodemographic and professional variables. Thus, education on mpox among healthcare providers in Ethiopia is critical in preparing the workforce and limiting potential damage to the country.

Development of a concentration method for simple and sensitive detection of SARS-CoV-2 in saliva using a magnetic nanoparticle kit

BackgroundWhen diagnosing viral infections in humans and animals, the presence of virus in a sample in trace amounts that are below the analytical sensitivity of the detection system may cause false negative results and inaccurate diagnosis. We previously reported the development of a simple virion concentration technique using 12 ml large-volume samples that can dramatically improve diagnostic sensitivity by increasing analytical sensitivity by 100-fold over conventional methods. The present study was conducted to further improve the simplicity and versatility of this method. We constructed a simple and highly sensitive method for the detection of SARS-CoV-2 in human saliva after concentration using a magnetic nanoparticle conjugated with polyethylene glycol (PEG). ResultsPerformance of the method was evaluated by comparing a combination of automated nucleic acid extraction and RT-qPCR or triplex RT-LAM detection in a spiked sample of 20 ml saliva collected from healthy humans. The method theoretically achieved 300-fold concentration of spiked SARS-CoV-2 in saliva, enabling 10- to 1000-fold higher analytical sensitivity for detection compared to conventional RNA extraction methods. ConclusionsThis newly developed method allows for easy and reliable concentration of the virion in less than 60 min, improving the analytical sensitivity of the SARS-CoV-2 test. Further, the method allows for easy and reliable enrichment of the virus in less than 60 min, improving the analytical sensitivity of the SARS-CoV-2 test. This method is easily used for highly sensitive virus detection from a variety of human oral fluid samples and may also be applied to rapid and labor-saving screening tests by pooling a large number of samples.

Single-cell transcriptomic analysis reveals the commonality of immune response upon H1N1 influenza virus infection in mice and humans

Seasonal influenza A virus (IAV), particularly the H1N1 subtype, poses a significant public health threat because of its substantial morbidity and mortality rates worldwide. Understanding the immune response to H1N1 is crucial for developing effective treatments and vaccines. In this study, we deciphered the single-cell transcriptomic landscape of peripheral blood mononuclear cells (PBMCs) from H1N1-infected humans and lung tissue samples from H1N1-infected mice by mining HIN1-related single-cell RNA sequencing data from the GEO database. We observed similar changes in immune cell composition following H1N1 infection, with an increase in macrophages but a decrease in T cells in both species. Moreover, significant transcriptional changes in bystander immune cells upon H1N1 infection were identified, with the upregulation of the chemokine CCL2 in human PBMCs and increased expression of interferon-stimulated genes such as Ifit3, Ifit1 and Isg15 in mouse pulmonary immune cells. Intercellular cross-talk analysis highlighted enhanced interactions among bystander immune cells during H1N1 infection, with neutrophils in humans and macrophages in mice showing the most remarkable increases in interaction intensity. Transcription factor analysis revealed the conserved upregulation of key antiviral regulons, including STAT1 and IRF7, in T cells across both species, highlighting their pivotal roles in antiviral defense. These results suggest that humans and mice exhibit common immune responses to H1N1 infection, underscoring the similarity of vital immune mechanisms across species. The conserved immune mechanisms identified in this study provide potential therapeutic targets for enhancing antiviral immunity. Our research underscores the importance of understanding species-specific and conserved immune responses to H1N1 and offers insights that could inform the development of novel antiviral therapies and improve clinical outcomes for individuals affected by influenza.

Human β-Defensin 2 as a Link between EBV Infection and Multiple Sclerosis

Multiple sclerosis (MS) is the result of a complex interaction between environmental factors and genetic predisposition. Epstein-Barr virus (EBV) is a significant environmental risk factor associated with MS. Human- beta defensin 2 (HβD-2) is a crucial innate immune response proteint that as an inflammatory marker protects humans from pathogens invading the body like viruses. Therefore, a case-control study was conducted on 90 subjected (48 patients with MS and 42 healthy controls) to examine the role of HβD-2 in EBV viral load infection and MS patients. An enzyme-linked immunosorbentassay kit was used to measure HβD-2 levels in serum. The viral load of EBV was determined using a real-time PCR. The findings revealed that median HβD-2 levels in patients were significantly lower than in controls. (96.62 vs.124.8 ng/mL; p &lt; 0.01). According to the receiver operating characteristic curve analysis, HβD-2 is good predictor for MS disease (area under the curve=0.739; p &lt; 0.001). EBV frequency was lower in MS patients compared to the controls, although difference was not statistically significant (25 vs. 38.1%; p = 0.181).On other hand, the median (EBV) load was substantially greater in patients than in healthy controls ( 8.55 vs. 1.4 DNA copy/100 cells). This study concluded that HβD-2 levels showed no significant differences in each age group, sex, Expanded Disability Status Scale (EDSS) of multiple sclerosis patients, rather showed an inverse significant correlation (correlation coefficient = - 0.432) with EBV load, which protect against human viral infections.

Prospects of Carica papaya in the treatment of human viral infections: A comprehensive and a systematic review

BackgroundViruses cause various human diseases, some of which become pandemic outbreaks lack effective treatments and vaccines. This study gathered data on Carica papaya's antiviral effects against various human viruses, highlighting its potential as a natural treatment. Through in-vitro, in-vivo, and clinical study analysis, we illustrated the potential of Carica papaya in combating viral infections and its potential role in cure of common viral diseases. Methodology: Research papers on antiviral activity of Carica papaya were identified by using specific keywords in PUBMED, Google Scholar, and ScienceDirect databases. Articles published between January 2015 and March 2024 were screened for inclusion. Eligible studies utilized Carica papaya leaves (powder or juice) or fruits to investigate their effects against human viral infections. Each selected study applied either qualitative or quantitative antiviral assays to assess the efficacy of Carica papaya in combating human viruses. ResultsFifteen studies went through assessment for antiviral properties of Carica papaya, 7 (46.67 %) of them displayed significant activity against the dengue virus, while 1 study (6.67 %) demonstrated moderate/less effectiveness against dengue serotype-2. Two studies (13.33 %) found no anti-dengue effects. Additionally, Carica papaya exhibited strong antiviral activity against SARS-CoV-2 in 2 studies (13.33 %). One study (6.67 %) showed inhibition of both dengue serotype-2 and chikungunya, and 1 study (6.67 %) each demonstrated inhibitory effects against human immunodeficiency virus and Zika virus infections. ConclusionThe present study listed human diseases for which Carica papaya revealed significant antiviral effects against Dengue virus, Severe acute respiratory syndrome, Human immunodeficiency virus-I, Chikungunya virus and Zika virus suggesting its potential as a treatment candidate for all these viruses. However, the majority of the research involved in-vitro screening, with minimal in-vivo and clinical testing. Further in-vivo studies and clinical trials should be conducted to explore the potential of Carica papaya in the treatment of human viral infections.

Current Nanotechnological Strategies for Delivery of Anti-Retroviral Drugs: Overview and Future Prospects

Abstract: Globally, over forty million people are living with Human Immunodeficiency Viral (HIV) infections. Highly Active Antiretroviral Therapy (HAART) consists of two or three Antiretroviral (ARV) drugs and has been used for more than a decade to prolong the life of AIDS-diagnosed patients. The persistent use of HAART is essential for effectively suppressing HIV replication. Frequent use of multiple medications at relatively high dosages is a major reason for patient noncompliance and an obstacle to achieving efficient pharmacological treatment. Despite strict compliance with the HAART regimen, the eradication of HIV from the host remains unattainable. Anatomical and Intracellular viral reservoirs are responsible for persistent infection. Elimination of the virus from these reservoirs is critical for successful long-term therapy. Therefore, innovative approaches are required to design safe and effective therapies. Nanotechnology has revolutionized HIV drug delivery by addressing key challenges, including improving drug solubility, targeting specific cells, extending drug release, protecting drugs from degradation, overcoming biological barriers, enabling combination therapy, and enhancing vaccine delivery. Several nanocarrier systems, such as dendrimers, nanoemulsions, liposomes, solid nanoparticles (SLNs), and nanostructured lipid carriers, have been proposed to treat HIV infection. Additionally, nanosuspensions of antiretroviral drugs offer promising strategies for improving treatment outcomes. While these advancements have significantly improved HIV management strategies, challenges remain, including unexpected toxicity, avoiding harmful biological interactions, and costs associated with the large-scale production of nanopharmaceuticals.

Subclinical myocardial disfunction detected by left ventricle myocardial work impairment in patients with long standing human inmmunodeficiency virus infection

Abstract Heart failure is a known complication in patients living with human inmmunodeficiency virus (HVI) infection. Detection of subclinical disfunction is nowadays possible by echocardiographic strain techniques. Myocardial work is a novel technique based on global longitudinal strain (GLS) that measures global work efficiency of left ventricle (GWE) and would allow early detection of subclinical myocardial damage. Methods We performed a cross sectional echocardiographic study of patients with long standing HIV infection, and no previous cardiopathy, assessing GLS of left ventricle (LV), left atrium (LA) and free wall of right ventricle (RV-FW GLS). We identified patients with subclinical disfunction expressed by an impaired GWE , and studied its determinants by lineal regression. Results 110 patients, 78.2% male, median age 53.3 (51.2-55.4) were included. Time from diagnosis was 20.5 (18.6-22.3) years. Myocardial work strain analysis showed an impaired GWE: 91.9% (90.9-92.9);p&amp;lt;0.001) and a GW index of 1840.8 mmHg%(1758.7-1922.9):p&amp;lt;0.001. The rest of deformation parameters laid into normal range: LV GLS was -19.5% (-19.0- -20.0) GLS dispersion 55.1 (50.1-60.1), LA GLS (reservoir) 32.8% (31.2-34.5), and RV free wall GLS -22.3% (-21.4 - -23.2). By univariate analysis, determinants of impaired GWE were age, Score2 risk, time from HIV diagnosis, QRS Interval duration, long QTc Interval, LV ejection fraction (LVEF),diastolic disfunction by doppler tissue imaging, CD4 count nadir, initial and maximun viral load, and exposure to didanosine treatment. After adjustment by cardiovascular risk and diastolic function (Ea velocity by tissue Doppler) , GWE impaired depended on duration of infection (Beta 0.3;95%CI:0.04-0.56;p=0.023), initial viral load (Beta -1.1;95%CI:-2.1- -0.02;p=0.046) and exposure to stavudine (Beta -6.3;95%IC: -11.5- -1.1;p=0.019). Conclusions Subclinical myocardial disfunction is prevalent in long standing HIV infection. Global work efficiency is a very sensitive parameter for detection, even in patients with normal GLS values, and it was related to duration of infection, initial viral load, and exposure to stavudine in our patients.Determinants of Global Work Efficiency

Development and Validation of a New Eco-Friendly HPLC-PDA Bioanalytical Method for Studying Pharmacokinetics of Seliciclib

Background and Objectives: Seliciclib (SEL) is the first selective, orally bioavailable potential drug containing cyclin-dependent kinase inhibitors. Preclinical studies showed antitumor activity in a broad range of human tumor xenografts, neurodegenerative diseases, renal dysfunctions, viral infections, and chronic inflammatory disorders. To support the pharmacokinetics and aid in therapeutic monitoring of SEL following its administration for therapy, an efficient analytical tool capable of quantifying the concentrations of SEL in blood plasma is needed. In the literature, there is no existing method for quantifying SEL in plasma samples. This study introduces the first HPLC method with a photodiode array (PDA) detector for the quantitation of SEL in plasma. Materials and Methods: The chromatographic resolution of SEL and linifanib as an internal standard (IS) was achieved on Zorbax Eclipse Plus C18 HPLC column (150 mm length × 4.6 mm internal diameter, 5 µm particle size), with a mobile phase composed of acetonitrile–ammonium acetate, pH 5 (50:50, v/v) at a flow rate of 1.0 mL min−1. Both SEL and IS were detected by PDA at 230 nm. The method was validated according to the ICH guidelines for bioanalytical method validation. Results: The method exhibited linearity in concentrations ranging from 50 to 1000 ng mL−1, with a limit of quantitation of 66.1 ng mL−1. All remaining validation parameters satisfied the ICH validation criteria. The environmental sustainability of the method was verified using three extensive tools. The proposed HPLC-PDA method was effectively utilized to study the pharmacokinetics of SEL in rats after a single oral administration of 25 mg/kg. Conclusions: The proposed method stands as a valuable tool for studying SELs for pharmacokinetics in humans. It aids in achieving the targeted therapeutic advantages and safety of treatment with SEL by optimizing the SEL dosage and dosing schedule.

MicroRNA let-7a regulation of Hantaan virus replication by Targeting FAS Signaling Pathways

Hantaan virus (HTNV) infection in humans can cause hemorrhagic fever and renal syndrome (HFRS). Understanding host responses to HTNV infection is crucial for developing effective disease intervention strategies. Previous RNA-sequencing studies have investigated the role of microRNAs (miRNAs) in the post-transcriptional regulation of host genes in response to HTNV infection. In this study, we demonstrated that HTNV infection induces let-7a expression in human umbilical vein endothelial cells (HUVEC) and that HTNV G protein upregulates the expression of let-7a. miRNA let-7a mimics and inhibitors validated the predicted targets, including cell apoptosis genes (FAS, caspase-8, and caspase-3) and inflammatory factors (IL-6 and its related factors). Modulation of miRNA let-7a levels by miRNA mimics and inhibitors affected HTNV replication, indicating that HTNV modulates host miRNA expression to affect the outcome of the antiviral host response.

The Resurgent Threat of Highly Pathogenic Avian Influenza HPAI A (H5N1) Virus: A Zoonotic Infectious Disease and Public Health Concern

The highly pathogenic avian influenza (HPAI) A (H5N1) virus of clade 2.3.4.4b was identified among waterfowl (wild birds and geese) and domestic poultry across Southeast Asia, Europe, and Africa in 2021. By 2022, the HPAI virus was detected in North America, signifying further global dissemination. There is no human immunity to clade 2.3.4.4b A (H5N1). With the spread of the A (H5N1) virus throughout the United States and increasing viral infection in humans, resurgence of the A (H5N1) virus is of great public health concern that it could lead to the next infectious zoonotic pandemic after Covid-19. This paper describes the characteristics of HPAI A (H5N1) virus of clade 2.3.4.4b and recommendations for clinical treatment and prevention.

Application of chimeric antigens to paper-based diagnostics for detection of West Nile virus infections of Crocodylus porosus – A novel animal test case

Laboratory-based diagnostics such as plaque reduction neutralisation tests (PRNT) and ELISA are commonly used to detect seroconversion to flavivirus infections. However, faster, qualitative screening methods are essential for quicker diagnosis and improved patient outcomes. Lateral flow assays (LFAs) offer rapid results (5–15 mins) at the point-of-care, but few commercial flavivirus antibody detection LFAs are available.We developed an LFA using novel chimeric viral antigens produced by genetically modifying the mosquito restricted Binjari virus (BinJV) to display the outer virion proteins of pathogenic viruses like West Nile virus (WNV). The BinJV chimeric platform offers several advantages for diagnostic assay development, including rapid construction of new chimeras in response to emerging viral variants, safe, scalable antigen manufacturing, and structural indistinguishability to the wild-type pathogenic virion.To demonstrate feasibility, we applied the chimeric WNV (BinJV/WNV) antigen to LFA as the capture/test line reagent for detecting seroconversion in crocodilians to WNV – a virus affecting crocodilians across multiple continents. We confirmed the antigenic conservation of the chimera on the LFA detection surface using monoclonal antibodies. Utilising well-characterised sera (n=60) from WNV-seropositive or flavivirus-naive Australian saltwater crocodiles (Crocodylus porosus), the assay exhibited 98.8 % sensitivity and 100 % specificity, with results obtained in under 15 minutes. The LFA also accurately detected seroconversion in animals experimentally infected with WNV.This qualitative screening method can be performed both inside and outside of a laboratory, and the assay design will guide the optimisation of similar tests for detecting vector-borne viral infections in humans and other animals.

MicroRNAs and human viral diseases: A focus on the role of microRNA-29

The viral replication can impress through cellular miRNAs. Indeed, either the antiviral responses or the viral infection changes through cellular miRNAs resulting in affecting many regulatory signaling pathways. One of the microRNA families that is effective in human cancers, diseases, and viral infections is the miR-29 family. Members of miR-29 family are effective in different viral infections as their roles have appeared in regulation of immunity pathways either in innate immunity including interferon and inflammatory pathways or in adaptive immunity including activation of T-cells and antibodies production. Although miR-29a affects viral replication by suppressing antiviral responses, it can inhibit the expression of viral mRNAs via binding to their 3′UTR. In the present work, we discuss the evidence related to miR-29a and viral infection through host immunity regulation. We also review roles of other miR-29 family members by focusing on their role as biomarkers for diagnosing and targets for viral diseases management.

The Impact of Climate on Human Dengue Infections in the Caribbean.

Climate change is no longer a hypothetical problem in the Caribbean but a new reality to which regional public health systems must adapt. One of its significant impacts is the increased transmission of infectious diseases, such as dengue fever, which is endemic in the region, and the presence of the Aedes aegypti mosquito vector responsible for transmitting the disease. (1) Methods: To assess the association between climatic factors and human dengue virus infections in the Caribbean, we conducted a systematic review of published studies on MEDLINE and Web of Science databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. (2) Results: In total, 153 papers were identified, with 27 studies selected that met the inclusion criteria ranging from the northern and southern Caribbean. Rainfall/precipitation and vapor pressure had a strong positive association with dengue incidence, whereas the evidence for the impact of temperatures was mixed. (3) Conclusions: The interaction between climate and human dengue disease in the Caribbean is complex and influenced by multiple factors, including waste management, infrastructure risks, land use changes, and challenged public health systems. Thus, more detailed research is necessary to understand the complexity of dengue within the wider Caribbean and achieve better dengue disease management.

Attenuated effector T cells are linked to control of chronic HBV infection

Hepatitis B virus (HBV)-specific CD8+ T cells play a dominant role during acute-resolving HBV infection but are functionally impaired during chronic HBV infection in humans. These functional deficits have been linked with metabolic and phenotypic heterogeneity, but it has remained unclear to what extent different subsets of HBV-specific CD8+ T cells still suppress viral replication. We addressed this issue by deep profiling, functional testing and perturbation of HBV-specific CD8+ T cells during different phases of chronic HBV infection. Our data revealed a mechanism of effector CD8+ T cell attenuation that emerges alongside classical CD8+ T cell exhaustion. Attenuated HBV-specific CD8+ T cells were characterized by cytotoxic properties and a dampened effector differentiation program, determined by antigen recognition and TGFβ signaling, and were associated with viral control during chronic HBV infection. These observations identify a distinct subset of CD8+ T cells linked with immune efficacy in the context of a chronic human viral infection with immunotherapeutic potential.