Viral immunology最新文献

Interleukin-35 (IL-35) has an immunosuppressive function through the regulation of immune cells during infectious diseases, autoimmune disorders, and cancers. The modulatory role of IL-35 in T lymphocytes, which are involved in host immune responses during human immunodeficiency virus-1 (HIV-1) infection, has not been elucidated. The aim of the current study was to investigate the role of regulatory function of IL-35 to T-cell activity in patients living with chronic HIV-1 infection. Sixty-seven patients living with chronic HIV-1 infection and 17 controls were enrolled in the study. IL-35 levels were measured via an enzyme-linked immunosorbent assay. Purified CD4⁺ and CD8⁺ T cells were stimulated with recombinant human IL-35. The secretion of cytokines and cytotoxic molecules, the mRNA levels of IL-35 receptor subunits and transcription factors, the expression of immune checkpoint molecules, and cell proliferation were assessed to evaluate the effect of IL-35 on T lymphocyte function in vitro. Compared with controls, patients living with chronic HIV-1 infection presented increased plasma IL-35 levels. IL-35 stimulation did not affect either the expression of IL-35 receptor subunits or the proliferation of CD4⁺ and CD8⁺ T cells from either patients living with chronic HIV-1 infection or controls. IL-35 stimulation downregulated transcription factor mRNA expression and cytokine secretion by CD4⁺ T cells as well as cytotoxic molecule production by CD8⁺ T cells from both patients living with chronic HIV-1 infection and controls. This process was accompanied by increased expression of immune checkpoint molecules on CD4⁺ and CD8⁺ T cells. The addition of IL-35 also reduced perforin and granzyme B secretion by HIV-1-specific CD8⁺ T cells from patients living with chronic HIV-1 infection. Increased plasma IL-35 in patients living with chronic HIV-1 infection might dampen the activation of CD4⁺ and CD8⁺ T cells, leading to T-cell exhaustion.

Respiratory syncytial virus (RSV) is a significant cause of disease in the young and old. Recently, pre-fusion F protein vaccines for RSV have received food and drug administration (FDA) approval to protect adults aged 60 years and older; however, vaccines evaluated against RSV typically do not elicit complete or durable protective immunity. We previously showed that an RSV G protein central conserved domain (CCD) nanoparticle vaccine containing an S177Q mutation (NP-S177Q) induced favorable immunogenicity and RSV-neutralizing antibodies compared with RSV G protein vaccination alone in mice. Boosting BALB/c mice with NP-S177Q vaccines improved correlates of protection and reduced markers of immunopathology following RSV challenge. This study examined microparticle (MP) vaccines displaying the CCD with an RSV G S177Q mutation (MP-S177Q) adjuvanted with monophosphoryl lipid A (MPLA) in BALB/c mice. Our findings show that mice adjuvanted MP-S177Q vaccination develop effective viral neutralization compared with MP-WT and MP-S177Q vaccination and have improved bronchoalveolar Th1-type cytokine responses following the RSV challenge compared with MP-WT or vehicle-vaccinated mice. This study shows that a rationally mutated RSV G protein MP vaccine is safe, effective, and can advance precision RSV vaccines.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, has been spreading and changing globally. Adjuvant-based vaccines can improve vaccine protection by enhancing the immune response. Bacterial flagellin is a potent adjuvant and promotes protective immune responses. Here, we successfully expressed and purified the S1 subunit of SARS-CoV-2. The adjuvanticity of flagellin (FliC) of Salmonella Typhimurium in mice was determined by combining it with the recombinant S1 subunit vaccine. FliC-adjuvanted S1 vaccine could induce significantly enhanced S1-specific Immunoglobulin G (IgG), IgG1 and IgG2a titers, SARS-CoV-2-neutralizing antibodies, and levels of Th1 type (TNF-α and IFN-γ) and Th2 type (Interleukin-5 (IL-5), IL-4, IL-10, and IL-13) cytokines in splenocytes compared with the S1 alone group. Additionally, the titers of S1-specific IgG antibodies in the FliC adjuvant group could maintain a high level for at least 2 months. These results indicated that the FliC-adjuvanted S1 subunit vaccine could trigger strong humoral and cellular immune responses, which could promote the ongoing development of COVID-19 vaccines.

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.