Viral immunology最新文献

The Heartland virus (HRTV) is a tick-borne human pathogenic phlebovirus that primarily causes leukopenia and thrombocytopenia. It is transmitted by Amblyomma americanum type of tick, that is, notable for their aggressive biting behavior, affinity for human hosts, and high prevalence. Developing vaccines or immunizations against HRTV is gaining importance as a public-health preventive strategy. The current study was planned to prioritize a multi-epitope stable mRNA vaccine model against HRTV from lead B-cell and T-cell epitopes (with IC₅₀ < 100 nM) of HRTV proteome following advanced immunoinformatics approaches. Model constructs were designed by linking the most potent, nonallergenic epitopes along with incorporation of human ribosomal protein adjuvant for immune response enhancement. The immunogenic potential of the coding vaccine molecule was examined via molecular docking against toll-like receptors immune receptors followed by normal mode analysis and molecular dynamics simulations-based energy minimization, molecular stability, and flexibility assessments. A robust, stable circular mRNA precursor of multi-epitopes vaccine model was designed by incorporating the Kozak consensus sequence, a start codon, and essential elements such as MHC class I trafficking domain (MITD), tPA, Goblin 5' and 3' Untranslated Region (UTRs), and a poly (A) tail. This strategic amalgamation ensures elevated immunogenicity and predicts a promising circular mRNA vaccine model against HRTV. The immune simulation predicted that the designed model vaccine is capable to elicit cell-mediated and humoral immune responses. The predicted circular mRNA vaccine precursor model is promising against HRTV to examine experimentally for its immunogenicity and safety features.

Dengue fever (DF) is a common mosquito-borne viral infection caused by any of the four dengue virus (DENV) serotypes. In recent years, the global incidence of DF has risen rapidly, which has widely threatened the health of millions of people in the United States, Southeast Asia, and the Western Pacific. The challenges for the prevention and control of DENV infection have become increasingly severe. Over the years, advances in the area of DF research have been continuously updating. In this review, we provide an updated and more in-depth overview of dengue epidemiology and pathogenesis, along with recent progress in diagnostic approaches (including methods to address cross-reactivity with other flaviviruses) and an expanded discussion of current dengue vaccine development, such as CYD-TDV (Dengvaxia), TV003/TV005, and the new TAK-003. This comprehensive perspective aims to offer references for the prevention, clinical diagnosis, and control of the disease.

Viral infections are ubiquitous, and their prevention and treatment have become a great challenge. Steroids have different biological activities, including antiviral activity, which is related to steroid structural diversity. With the intensive study of steroids, it has been found that steroids can interfere with almost any step of the viral life cycle to exert antiviral activity. In this article, we review the antiviral activity and mechanism of action of steroids and their derivatives against a range of human viruses and conclude that natural steroids and their derivatives are very promising antiviral drug candidates that deserve further study to elucidate their pharmacological potential.

Interferon (IFN) is a pivotal agent against hepatitis B virus (HBV) in clinic, but there is a lack of accurate biomarkers to predict the response to IFN therapy in patients with chronic hepatitis B (CHB). Our study aimed to investigate potential targets for IFN therapy and to explore the network of interactions associated with IFN response. MicroRNA (miRNA) (GSE29911) and messenger RNA (GSE27555) datasets were used to screen the differentially expressed miRNAs (DEmiRNAs) and differentially expressed genes (DEGs). The random forest and k-nearest neighbors algorithm were used to further screen the core DEmiRNAs and build a prediction model. A Protein-Protein Interaction (PPI) network based on the STRING database was constructed and visualized by the Cytoscape software. Then, we collected transcription factors (TFs) from the TransmiR database to construct the TF-miRNA-hub gene regulatory network. Finally, real-time quantitative polymerase chain reaction was used to verify the expression of four miRNAs in HepG2-NTCP and Huh-7, and the effect of IFN treatment on four miRNAs' expression was preliminarily explored. Eighteen DEmiRNAs in GSE29911 and 700 DEGs in GSE27555 were identified. Boruta feature selection identified four miRNAs (miR-873, miR-200a, miR-30b, and let-7g) from 18 DEmiRNAs. We identified 48 TFs, 4 miRNAs, and 10 hub genes and constructed a TF-miRNA-hub gene network to suggest the mechanism of IFN response. According to the experimental results, miR-873 was upregulated and IFN treatment could inhibit it in HBV-transfected cells (p < 0.05). We constructed a TF-miRNA-hub gene regulatory network, and our results demonstrate that miR-873 was identified as a potential biomarker of IFN response in patients with CHB. This information provides an initial basis for understanding the complex IFN response regulatory mechanisms.

People living with HIV (PLWH) beginning antiretroviral therapy (ART) retain a high burden of cytomegalovirus (CMV). CMV has been implicated in atherosclerosis in healthy adults, and a role in PLWH is plausible. Atherosclerosis has also been linked with γδ T cells and CMV seropositivity with altered γδ T cell profiles in other populations. In our cohort of PLWH starting ART in Jakarta (Indonesia), metrics of the CMV burden correlated with altered profiles of Vδ2^- γδ T cells. Here CMV DNA was sought by RT-PCR as PLWH began ART. γδ T cell subsets were immunophenotyped using flow cytometry, and CMV-reactive antibodies were quantitated by ELISA after fixed intervals on ART. Carotid intima-media thickness (cIMT) was used to assess atherosclerosis. PLWH retained higher levels of CMV-reactive antibody than healthy controls (p = 0.001-0.04), and 50% began ART with detectable CMV DNA. cIMT values rose between 6 and 12 months on ART. At 6 months, cIMT correlated with CMV-reactive antibodies and proportions of activated Vδ2^- γδ T cells (r = 0.56-0.57; p = 0.035-0.042) in PLWH who began ART with detectable CMV DNA. Hence, a high burden of replicating CMV may promote atherosclerosis in PLWH after a period on ART, and the role of activated Vδ2^- γδ T cells warrants further study.

Chronic hepatitis C virus (HCV) infection poses a major health risk worldwide, with patients susceptible to liver cirrhosis and hepatocellular carcinoma. This study focuses on the development of effective therapeutic strategies for HCV infection through the investigation of immunogenic properties of a DNA construct based on the NS3/4A gene of HCV genotype (g)3a. Gene expression of the mutagenized (mut) NS3/4A target genes was assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Additionally, bioinformatics tools were employed to evaluate the impact of the mut-NS3/4A-based DNA vaccine. Analysis revealed increased mut-NS3/4A mRNA levels and target protein abundance compared with the native sequence. Elevated mut-NS3/NS4A levels could result from increased RNA stability and proper protein folding. Physicochemical analyses of the protein demonstrated favorable attributes such as thermostability and solubility. Three-dimensional mut-NS3/4A protein modeling confirmed its high stability and agreement with known protein structures. Additionally, potential immunogenic regions of both T and B cell epitopes were discovered based on peptide binding to major histocompatibility complex molecules of Asian origin. Importantly, these epitopes exhibited nonallergenic and nontoxic characteristics. These findings highlight the potential of the NS3/4A-based DNA construct as a promising candidate for an HCVg3a vaccine tailored for the Asian population, providing valuable insights for future immunotherapeutic approaches.