Search Results (1,787)

Vaccination is the most effective method to counteract infectious diseases in farmed fish. It secures aquaculture production and safeguards the wild stock and aquatic ecosystem from catastrophic contagious diseases. In vaccine development, recombinant subunit vaccines are favorable candidates since they can be economically produced in large quantities without growing many pathogens, as in inactivated or attenuated vaccine production. However, recombinant subunit vaccines are often weak or deficient in immunogenicity, resulting in inadequate defenses against infections. Technologies that can increase the immunogenicity of recombinant subunit vaccines are in desperate need. Enhanced green fluorescence protein (EGFP) has a low antigenicity and is susceptible to folding changes and losing fluorescence after fusing with other proteins. Using these valuable features of EGFP, we comprehend two amphipathic alpha-helical peptides, AH1 and AH3, derived from Hepatitis C virus and Influenza A virus, respectively, that can induce high immune responses of their fused EGFP in fish without affecting their folding. AH3-EGFP has the most elevated cell binding, significantly 62% and 36% higher than EGFP and AH1-EGFP, respectively. Immunizations with AH1-EGFP or AH3-EGFP significantly induced higher anti-EGFP antibody levels 300–500-fold higher than EGFP immunization after the boost injection in rainbow trout. Our results suggest that AH1 and AH3 effectively increase the immunogenicity of EGFP without influencing its structure. Further validation of their value in other recombinant proteins is necessary to demonstrate their broader utility in enhancing the immunogenicity of subunit vaccines. We also suggest that EGFP and its variants are promising candidates for initially screening proper immunogenicity-enhancing peptides or proteins to advance recombinant subunit vaccine development. Full article

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

The precipitation of cryoglobulins, serum immunoglobulins, below 37 °C defines the clinical cryoglobulinemic syndrome, a systemic vasculitis usually characterized by purpura, weakness, and arthralgia. In most cases, this condition is associated with chronic infection by the hepatitis C virus (HCV) and can evolve into B-cell dysregulation and malignancies. The current literature on non-HCV-associated cryoglobulinemia is very limited, and little is known about the immunological and serological profile of affected patients. The cryoglobulinemic syndrome not associated with HCV infection is often found concomitantly with other infections, autoimmune diseases, and B-cell lymphoproliferative disorders. The cryoprecipitation of fibrinogen has been described as a rare disorder, perhaps underestimated and not fully understood, causing thrombotic occlusion and ischemia in different rheumatic disorders. Cold temperature plays a pathogenetic role in autoimmune hemolytic anemias, in which the presence of cold agglutinins produced by B cells at the lymphoplasmacytic cell stage may promote agglutination of red blood cells in the coldest parts of the circulation, even at mild room temperatures, undergoing hemolysis. Laboratory methods for the detection and quantification of cryoproteins are downright critical, and their concurrent detection is pivotal for the diagnosis. In this review, we summarize the clinical involvement of cryoglobulins, cryofibrinogen, and cold agglutinins in non-HCV autoimmune diseases, underlining the crucial steps of the most employed analytic methods. Full article

The global elimination of hepatitis C virus (HCV) has been prioritized by the World Health Organization (WHO) as a key public health target, with a deadline set for 2030. This initiative aims to significantly reduce both new infection rates and HCV-associated mortality. A major breakthrough in achieving this goal has been the development of direct-acting antiviral agents (DAAs), which offer cure rates exceeding 95%, along with excellent safety and tolerability. Nevertheless, transmission via parenteral routes continues to be the dominant pathway, particularly among high-risk groups, such as individuals who inject drugs, incarcerated populations, those exposed to unsafe medical practices, and healthcare professionals. Identifying, monitoring, and delivering tailored interventions to these groups is crucial to interrupt ongoing transmission and to reduce the burden of chronic liver disease. On a global scale, several nations have demonstrated measurable progress toward HCV elimination, with some nearing the targets set by WHO. These achievements have largely resulted from context-adapted policies that enhanced diagnostic and therapeutic access while emphasizing outreach to vulnerable communities. This review synthesizes current advancements in HCV prevention and control and proposes strategic frameworks to expedite global elimination efforts. Full article

Co-infections pose significant challenges not only clinically, but also in terms of simultaneous diagnoses. The development of sensitive, multiplexed analytical platforms is critical for accurately detecting viral co-infections, particularly in complex biological environments. In this study, we present a mass spectrometry (MS)-based detection strategy employing a target-triggered hybridization chain reaction (HCR) to amplify signals and in situ photocleavable mass tags (PMTs) for the simultaneous detection of multiple targets. Hairpin DNAs modified with PMTs and immobilized loop structures on magnetic particles (Loop@MPs) were engineered for each target, and their hybridization and amplification efficiency was validated using native polyacrylamide gel electrophoresis (PAGE) and laser desorption/ionization MS (LDI-MS), with silica@gold core–shell hybrid (SiAu) nanoparticles being employed as an internal standard to ensure quantitative reliability. The system exhibited excellent sensitivity, with a detection limit of 415.12 amol for the hepatitis B virus (HBV) target and a dynamic range spanning from 1 fmol to 100 pmol. Quantitative analysis in fetal bovine serum confirmed high accuracy and precision, even under low-abundance conditions. Moreover, the system successfully and simultaneously detected multiple targets, i.e., HBV, human immunodeficiency virus (HIV), and hepatitis C virus (HCV), mixed in various ratios, demonstrating clear PMT signals for each. These findings establish our approach as a robust and reliable platform for ultrasensitive multiplexed detection, with strong potential for clinical and biomedical research. Full article

The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. Full article

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection. Full article

Coinfections with hepatitis C virus (HCV) or human immunodeficiency virus (HIV) among individuals with chronic hepatitis B (CHB) are associated with worse clinical outcomes but remain understudied due to their low prevalence and the sensitivity of associated data. This nationwide, cross-sectional study utilized claims data from the Korean Health Insurance Review and Assessment Service (2014–2021) to investigate the prevalence, comorbidities, treatment patterns, and liver-related complications among patients with HBV monoinfection, HBV/HIV, HBV/HCV, or triple coinfection. Among over 4.5 million patients with chronic hepatitis B, the prevalence of HIV and HCV coinfection ranged from 0.05 to 0.07% and 0.77 to 1.00%, respectively. Patients with HBV/HCV coinfection were older and had significantly higher rates of hypertension, diabetes, dyslipidemia, and major adverse liver outcomes, including hepatocellular carcinoma and liver transplantation, compared to other groups. HBV/HIV coinfection was more common in younger males and was associated with higher dyslipidemia. The use of HBV antivirals increased over time across all groups. These findings highlight the distinct clinical characteristics and unmet needs of coinfected populations, underscoring the importance of tailored screening and management strategies in HBV-endemic settings. Full article

Hepatitis E virus (HEV) is a pathogen that has caused various epidemics and sporadic localized cases. It is considered to be a public health problem worldwide. HEV is a small RNA virus with a significant genetic diversity, a broad host range, and a heterogeneous geographical distribution. HEV is mainly transmitted via the faecal–oral route. However, some animals are considered to be natural or potential reservoirs of HEV, thus elucidating the zoonotic route of transmission via the environment through contact with these animals or consumption of their by-products. Other routes of human-to-human transmission are not negligible. The various human–animal–environment entities, taken under one health approach, show the circulation and involvement of the different species (mainly Paslahepevirus balayani and Rocahepevirus ratti) and genotypes in the spreading of HEV infection. Regarding P. balayani, eight genotypes have been described, of which five genotypes (HEV-1 to 4 and HEV-7) are known to infect humans, while six have been reported to infect animals (HEV-3 to HEV-8). Furthermore, the C1 genotype of the rat HEV strain (HEV-C1) is known to be more frequently involved in human infections than the HEV-C2 genotype, which is known to infect mainly ferrets and minks. Contamination can occur during run-off, flooding, and poor sanitation, resulting in all of these genotypes being disseminated in the environment, contaminating both humans and animals. This systematic review followed the PRISMA guidelines and was registered in PROSPERO 2025 CRD420251071192. This research highlights the importance of investigating the transmission routes and major circulating HEV genotypes in order to adopt a holistic approach for controlling its emergence and preventing future outbreaks. In addition, this article outlines the knowledge of HEV in Africa, underlining the absence of large-scale studies at the environmental, human, and animal levels, which could improve HEV surveillance on the continent. Full article

Polyphenols are structurally diverse plant metabolites that have attracted significant interest. Their compositions are versatile, depending on their structures, including the number of rings in the polyphenol composition. Based on these attributes, polyphenols can be classified as flavanols, anthocyanins, flavones, phenolic acids, stilbenes, and lignans. Polyphenols mainly possess inhibition of viral replication, interference with viral protein synthesis, and modulation of immune responses, providing significant antiviral effects against several viruses, including herpes simplex virus, hepatitis C virus, and influenza. They are crucial for medical compounds in diverse, versatile treatments, namely in diabetes, cardiovascular disorders, cancer, and neurodegenerative problems. Plants are the primary source of bioactive molecules, which are valued for their anti-inflammatory, antioxidant, anticancer, and antiviral activities. Especially, polyphenols are extracted as the most abundant bioactive compounds of plants. Moreover, viral infections are one of the major factors in illnesses and diseases, along with bacteria and fungi. Numerous in vitro and in vivo studies report antiviral activity against SARS-CoV-2, Mayaro virus, dengue virus, herpesvirus, and influenza A virus, though clinical validation remains limited. Additionally, inhibition of viral entry, interference with viral replication, modulation of host immune response, and direct virucidal effects were examined. Full article

Hepatitis C is an infectious liver disease which contributes to an estimated 400,000 deaths each year. The disease is caused by the hepatitis C virus (HCV) and is spread by direct blood contact between infected and susceptible individuals. While the magnitude of its impact on human populations has prompted a growing body of scientific work, the current epidemiological models of HCV transmission among injecting drug users treat risk behaviors as fixed parameters rather than as outcomes of a dynamic, decision-making process. Our study addresses this gap by constructing a game-theoretic model to investigate the implications of voluntary participation in clean needle exchange programs on the spread of HCV among this high-risk population. Individual drug users weigh the (perceived) cost of clean equipment usage relative to the (perceived) cost of infection, as well as the strategies adopted by the rest of the population, and look for a selfishly optimal level of protection. We find that the spread of HCV in this population can theoretically be eliminated if individuals use sterile equipment approximately two-thirds of the time. Achieving this level of compliance, however, requires that the real and perceived costs of obtaining sterile equipment are essentially zero. Our study demonstrates a robust method for integrating game theory with epidemiological models to analyze voluntary health interventions. It provides a quantitative justification for public health policies that eliminate all barriers—both monetary and social—to comprehensive harm-reduction services. Full article

Current structural barriers experienced by First Nations in Canada shape access and engagement for testing and treatment of hepatitis C virus (HCV) infections. This non-systematic informative review considers transdisciplinary perspectives, regional data, and published literature connecting context to the disproportionate HCV burden experienced by First Nations populations in the prairie provinces of Canada, and offers examples of participatory and community-led initiatives working toward the elimination of HCV as a public health threat. First Nations in Canada are disproportionately impacted by chronic HCV infection, with a reported rate of newly diagnosed HCV cases in First Nations communities five times the respective rate in the general Canadian population in 2022. This review explores the reasons underlying the disproportionate burden of HCV infection. Significant over-representation of First Nations in the Canadian Prairies is seen in the major risk categories for HCV acquisition, and the impact of these risk factors is aggravated by barriers to accessing healthcare services and medication coverage. These barriers stem from the legacy of colonialism, discrimination, disenfranchisement, and are exacerbated by stigmatization, victimization, and racism in the justice and healthcare systems. Other contributory factors that impede access to care include inadequate healthcare clinic staffing and infrastructure in First Nations communities, and significant geographical distances between First Nations reserves and laboratories, pharmacies, and treating/prescribing healthcare providers. Recent recognition of historical harms and early steps towards nation-to-nation reconciliation, along with support for culturally connected, holistic, and First Nations-led wellness programs, instill hope that elimination strategies to eradicate HCV infection in First Nations populations will be successful in Canada. Full article

Chronic hepatitis B virus (CHB) infection remains a leading cause of hepatic inflammation and damage. Several studies have suggested the significant role of CX3C chemokine receptor 1 (CX3CR1) in inflammatory damages. The polymorphisms V249I and T280M affect receptor expression and function. In the current study, we investigated the association of V249I and T280M variants of the CX3CR1 fractalkine receptor with susceptibility to CHB disease. In total, 280 patients with chronic hepatitis B and 260 controls from different cities of Tunisia recruited in the Pasteur Institute of Tunisia between January 2017 and December 2022 were genotyped for the V249I and T280M CX3CR1 gene. The allele and genotype frequencies of these variants did not show significant associations with susceptibility to CHB infection (p > 0.05). Analysis of allele and genotype frequencies showed that there was no differences in age and sex distribution between patients and the control group, but when CHB patients were stratified according to age, a clear significant difference was obtained for the T280M polymorphism (p < 10⁻³, OR = 88.91; p < 10⁻³, OR = 37.42, for genotype and allelic distribution, respectively) with the MM genotype being more frequent in patients aged ≥ 50 years. The most frequently combined genotypes in the Tunisian population were VVTT, VITT and VITM both in patients (48.9%, 22.5% and 22.1%, respectively) and in controls (52%, 23.8%, 13.5%, respectively) compared to the extremely rare IITT, IITM or IIMM genotypes. In conclusion, this study suggests a noteworthy genotype–age association, particularly involving the T280M variant Full article

Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To improve the clinical relevance of TTV quantification, in this study, we investigated the use of PMAxx™, a virion viability dye that selectively blocks the amplification of compromised virions. Serum samples from 10 Hepatitis C Virus-positive (HCV+) individuals, 81 liver transplant recipients (LTRs), and 40 people with HIV (PWH) were treated with PMAxx™ and analyzed for TTV DNA loads by digital droplet PCR (ddPCR). Furthermore, anti-SARS-CoV-2 IgG levels and neutralizing antibody (nAbs) titers were measured post-COVID-19 vaccination. Using ddPCR, the PMAxx™ treatment significantly reduced the TTV DNA levels in all the groups (mean reduction: 0.66 Log copies/mL), indicating the abundant presence of non-intact, circulating viral genomes. However, correlations between TTV DNA and SARS-CoV-2 IgG or nAbs were weak or absent in both PMAxx™-treated and untreated samples. These findings suggest that while PMAxx™ enhanced the specificity of TTV quantification, it did not improve the predictive value of TTV viremia at assessing vaccine-induced humoral responses. Full article

Hepatitis C virus (HCV) infection is a major public health concern, with more than 58 million people chronically infected worldwide. The management of HCV, once the domain of specialists only, has been revolutionized by the advent of direct-acting antiviral therapies. To reduce the burden of HCV in the United States (US), emphasis is now being placed on the involvement of primary care physicians in the management of HCV patients. Inclusion of more primary care providers in the HCV diagnosis and treatment initiatives can assist in achieving the goal of HCV elimination, especially in the medically underserved areas. To actively engage in the management of HCV, primary care providers must understand its epidemiology, risk factors, natural history, current treatment regimen, and potential complications. This manuscript reviews these key areas, along with presenting the cost-effectiveness of treatment and evidence-based guidelines for follow-up care in adults with chronic HCV infection who have undergone HCV treatment. Equipped with this foundational knowledge about HCV management, primary care physicians can play a vital role in eliminating HCV. Full article