Viral immunology最新文献

The rapid evolution of viral pathogens presents significant challenges for global health, as traditional methods for virus detection often fail to identify novel or genetically diverse viruses. The emergence and reemergence of viral pathogens necessitate more advanced and inclusive diagnostic approaches. This review aims to explore the role of metagenomics in overcoming the limitations of traditional viral detection methods and to assess its impact on the discovery, characterization, and surveillance of viral pathogens. A comprehensive review of recent studies employing metagenomic approaches to viral detection was conducted. High-throughput sequencing technologies and bioinformatics tools were highlighted as key components in enabling broad-spectrum viral identification and characterization. Metagenomic approaches have successfully identified novel pathogens, including new arboviruses and reemerging strains of known viruses. These techniques provide a more complete understanding of viral diversity and dynamics, surpassing the limitations of targeted assays and culturing methods. Key findings emphasize the capability of metagenomics to detect viruses previously undetected by conventional methods, improving the scope of surveillance. Metagenomics offers transformative advantages for viral surveillance and outbreak management. It enhances early detection, allows for better-informed responses to viral threats, and contributes to more effective strategies for managing emerging and reemerging viral pathogens. Integration of metagenomic techniques into public health practices is crucial for combating the evolving landscape of viral diseases.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global health crisis by triggering extensive systemic and immune dysregulation. Granulocytes, including neutrophils, eosinophils, and basophils, are critical components of the innate immune system that play dual roles in protection and pathogenesis during infection. In this review, we examine the multifaceted roles of granulocytes in COVID-19 and their impact on disease severity through excessive inflammation, cytokine storm, and tissue damage. Neutrophil extracellular traps (NETs) and the overactivation of neutrophil subtypes contribute to the development of thrombosis and acute respiratory distress syndrome. In contrast, eosinophils and basophils modulate T helper 2-type and allergic responses that may influence recovery or disease progression. We further summarize the therapeutic strategies targeting granulocyte activation and signaling pathways, including IL-1, IL-6, IL-17, IL-5 receptor, granulocyte-macrophage colony-stimulating factor inhibitors, and antihistamines, emphasizing their clinical outcomes, approval status, and the global regions in which they are studied. Understanding the regulatory mechanisms of granulocyte activation and inhibition provides new insights into COVID-19 immunopathology and opens pathways for targeted immunomodulatory therapy. These findings underscore the importance of balancing protective immune functions with controlled anti-inflammatory interventions to mitigate the severe complications of SARS-CoV-2 infection.

The immunological properties of recombinant hepatitis B surface antigen (rHBsAg), prepared using yeast (Saccharomyces cerevisiae [SC]) and Chinese hamster ovary (CHO) cells, were evaluated through in vitro and in vivo assays to support the efficacy of recombinant hepatitis B vaccines. In vitro, antigenicity was assessed by measuring the affinity of rHBsAg to anti-HB antibodies using surface plasmon resonance. In vivo, mice were intraperitoneally injected with 3 µg of simulated vaccines containing anti-HB antibodies absorbed onto aluminum hydroxide adjuvant. Humoral responses were evaluated by measuring serum anti-HB antibody titers and seroconversion rates on days 7, 14, 21, and 28. Cellular immune responses were assessed based on cytokine (Interferon-γ-IFN-γ) and (Tumor Necrosis Factor-α- TNF-α) production from splenic lymphocytes on day 28 postimmunization. A recombinant Huh-7-HBsAg cell line, developed to analyze cellular immune responses, was established through cytotoxicity and apoptosis assays. In vitro, the equilibrium dissociation constant (K_D) of rHBsAg from CHO cells was significantly lower than that from yeast cells, indicating stronger antibody affinity. In vivo, rHBsAg-CHO induced faster and higher antibody titers compared with rHBsAg-SC. Cellular responses showed higher levels of TNF-α and IFN-γ for rHBsAg-CHO. In addition, the rHBsAg-CHO group exhibited higher late apoptosis rates in target cells. The rates induced in the rHBsAg-CHO and rHBsAg-SC groups were 25.0% and 19.2%, respectively. In conclusion, this study demonstrates that the immunological properties of rHBsAg vary based on the expression systems and provides nonclinical data supporting the evaluation of vaccine efficacy.

As a key component of innate immunity, natural killer (NK) cells initiate rapid effector responses against various viral pathogens. However, their role in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS) remains unclear. In this study, NK cell subsets and receptor expression were analyzed by flow cytometry in patients with HFRS. Enzyme-linked immunosorbent assay was used to measure soluble HLA-G (sHLA-G) levels in plasma. In experimental models of acute viral infection, changes in the expression of several NK cell receptor ligands were also detected by flow cytometry. Flow cytometry revealed a redistribution of NK cell subsets in patients with HFRS, characterized by the expansion of CD56⁺CD16^- NK cells, which remained elevated from the acute phase to the convalescent phase. In addition, sustained overexpression of NK cell receptors (NCR p30⁺, NCR p44⁺, NCR p46⁺, KIR2DL2/3, and KIR2DL4) was observed beyond the acute phase. Higher plasma concentrations of sHLA-G were detected in mild-type cases compared with moderate-type, severe-type, and critical-type patients. Hantaan virus infection was also found to upregulate intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD62E, CD62P, human leukocyte antigen-A, B, C (HLA-A, B, C), HLA-E, and HLA-G. These findings suggest that NK cells undergo rapid expansion following viral infection and maintain elevated levels throughout the clinical course, accompanied by persistent overexpression of NK receptors. Lower concentrations of soluble HLA-G (sHLA-G) in moderate-type, severe-type, and critical-type patients may indicate a potential mechanism contributing to increased vascular permeability in HFRS.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne SFTS virus (SFTSV), with a case fatality rate of 16.2-32.6% in East Asia. Currently, no approved vaccines or antiviral treatments exist. Monoclonal antibody (mAb) therapy offers rapid immune protection and is a promising strategy against SFTSV. This review outlines advances in SFTSV neutralizing mAb research, covering conventional generation methods (hybridoma, phage display) and innovative approaches such as single B cell sequencing. We also introduce computational tools like artificial intelligence -assisted epitope prediction and in silico mAb design. Furthermore, we discuss the structure-function relationships of mAbs targeting Gn and Gc glycoproteins, their mechanisms (e.g., fusion inhibition, receptor blockade), and key functional attributes including breadth, potency, and cross-reactivity. Challenges such as limited epitope accessibility, immune interference, and antibody-dependent enhancement are highlighted. Finally, we propose a multipronged strategy integrating structure-guided engineering, high-throughput screening, and rigorous preclinical evaluation to accelerate the development of safe and effective SFTSV therapeutics.

The hepatitis delta virus (HDV) is a defective and small, blood-borne viroid-like pathogen that coinfects with the hepatitis B virus (HBV) in about 5% of the infected individuals as it is a satellite virus of HBV. The treatment of HDV infection is quite challenging because there is no vaccine against HDV. Several commercial PCR and in-house assays have been developed, but there are greater variations in the results of these assays because they are not standardized properly. Studies are also delayed because of the unavailability of commercial HDV-specific antibodies for the diagnosis of HDV infection, even for the research devotions. To fill this gap, the recombinant antigenic HDAg protein of genotype I of HDV from the local isolate was successfully expressed and purified in the Escherichia coli (E. coli) system, followed by anti-HDAg antibodies production in rabbits. After determining and amplifying the antigenic region of HDAg of HDV, the fragment was cloned into the pET-28a vector and expressed in E. coli TOP10 cells. Following the successful expression of recombinant HDAg protein with a His-tag at its C-terminal end, we purified the HDAg protein using affinity chromatography. Both the expression and purification of HDAg-An protein were confirmed through SDS-PAGE and Western blot analysis. Through proper optimization, the HDAg-An protein was obtained with more than 90% purity. The next step involved immunizing Japanese White rabbits with the purified HDAg. The immunization protocol included 80 µg of HDAg-An in two subcutaneous priming doses and four 40 µg booster doses, followed by blood collection two weeks after each boost to monitor antibody production. The level of anti-HDAg antibodies in the rabbit serum was assessed using a quantitative ELISA technique. In the future, these antibodies could be used for the development of HDV-specific in-house assays as well as vaccines against the HDV genotype I that is locally predominant, potentially decreasing the burden of imported diagnostic tools and reagents.

Background: Interleukin-37 (IL-37) can prevent liver damage and may be an important candidate for use as a novel therapeutic tool in hepatitis B virus (HBV) infection. This study aimed to evaluate the serum levels of IL-37 in individuals with chronic HBV (CHB) infection, those who spontaneously cleared (SC) HBV infection, compared with healthy control (HC) subjects. Materials and Methods: This case-control study included 30 patients with CHB (17 males, 13 females; mean age, 50.13 ± 14.51), 30 subjects with SC HBV infection (16 males, 14 females; mean age, 51.50 ± 16.85), and 42 HC subjects (22 males, 20 females; mean age, 53.52 ± 14.44). Blood samples were collected, and then serum IL-37 levels were measured using an enzyme-linked immunosorbent assay kit. Results: Our results showed that serum IL-37 levels were significantly higher in the CHB (96.99 ± 13.39 pg/mL) than in the HC group (37.85 ± 2.99 pg/mL, p = 0.02). No statistically significant differences were found in IL-37 serum levels between CHB group and SC group (91.93 ± 17.11 pg/mL, p = 0.43). Correlation analysis showed a significant negative correlation between serum IL-37 levels and age in SC subjects (p = 0.02, R = -0.42). Conclusion: Our results suggest that increased production of IL-37 may biologically act as a negative feedback loop to attenuate the release of pro-inflammatory cytokines and subsequently alleviate disease symptoms in CHB. The negative correlation between the cytokine and age may indicate that higher levels of IL-37 in younger individuals may lead to the spontaneous clearance of HBV.

The objective of this study is to examine the general characteristics, clinical manifestations, laboratory findings, and imaging features of patients with lung adenocarcinoma who develop influenza pneumonia while undergoing immunotherapy. A retrospective analysis was conducted on the clinical data of 48 patients with lung adenocarcinoma and pulmonary infections who received immunotherapy as a stand-alone treatment between September 2022 and September 2024 at the Affiliated Hospital of North China University of Science and Technology. Clinical characteristics of patients with concurrent influenza pneumonia were assessed. When compared with the non-influenza pneumonia group, patients in the influenza pneumonia group demonstrated significantly more severe systemic symptoms, elevated urea nitrogen levels, reduced platelet counts, decreased serum albumin levels, lower Prognostic Nutritional Index values, and higher prevalence of bilateral and multilobed lung involvement. Chest imaging frequently revealed ground glass opacities, reticular patterns, and the "crazy paving" sign. Additionally, this group exhibited higher CURB-65 scores and an increased need for intensive care unit admission, with all comparisons yielding p values <0.05. Hypotension emerged as a potential factor influencing mortality in both groups (odds ratio = 9.094, p = 0.041). Among the 19 patients with lung adenocarcinoma and influenza pneumonia, 89.5% had coinfections with other pathogens. Gram-negative bacterial infections were the most common (64.7%), with Klebsiella pneumoniae subspecies, Pseudomonas aeruginosa, and Haemophilus parainfluenzae identified as the leading pathogens. Fungal infections, primarily involving Aspergillus species, accounted for 23.5% of cases. General characteristics, clinical manifestations, laboratory findings, and imaging features are essential references for the diagnosis and management of lung adenocarcinoma complicated by influenza pneumonia. Particular attention should be directed to blood pressure fluctuations, with careful monitoring of low blood pressure, especially when accompanied by bacterial infections.

Background: In a subgroup of patients, coronavirus disease (COVID)-19 is a severe illness with high mortality due to hyperinflammation, development of acute respiratory distress syndrome, and multiorgan dysfunction syndrome. Complement system activation plays a critical role in the pathogenesis and severity of COVID-19 disease. Methods: This cross-sectional, single-center study aimed to investigate the correlation between serum C3 and C4 levels and COVID-19 severity. We included 125 patients hospitalized between December 2020 and March 2021. Patients were stratified into three groups based on the level of respiratory support needed to maintain adequate oxygenation (PaO₂ ≥ 60 mmHg): 51 patients requiring oxygen supplementation up to 15 L/min, 51 patients requiring high-flow oxygen therapy, and 23 patients requiring mechanical ventilation (MV). We analyzed the blood counts and serum levels of C3, C4, C-reactive protein (CRP), IL-6, procalcitonin, d-dimers, high-sensitive troponin I (TnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), IgA, IgG, IgM, C3, C4, rheumatoid factor, and anticitrullinated peptide antibodies. Results: Patients on MV had significantly lower levels of C3 and C4 (0.98 ± 0.24 g/L for C3 and 0.21 ± 013 g/L for C4) compared with patients with less severe disease (p < 0.001 for C3, p < 0.001 for C4). Serum C3 and C4 levels were lower in patients requiring high-flow oxygen therapy than in those requiring oxygen supplementation, however, the difference was not statistically significant. In addition, higher neutrophil counts were observed in patients on MV or high-flow oxygen therapy than in those on oxygen supplementation, and higher CRP, procalcitonin, and NT-proBNP levels were observed only in patients on MV. The levels of IL-6, d-dimers, and high-sensitive TnI were positively correlated with disease severity, whereas lymphocyte counts showed a negative correlation, and these differences were statistically significant among all three groups. Conclusion: The determination of serum levels of C3 and C4, along with other known laboratory risk factors, may contribute to the detection of patients at an increased risk for severe COVID-19.

To assess the dynamics of humoral immune responses to inactivated SARS-CoV-2 vaccines across populations with and without prior COVID-19 infection, a longitudinal cohort study was conducted. A total of 38 COVID-19-recovered individuals and 165 naïve participants (without prior COVID-19 infection) were enrolled, all of whom completed a two-dose vaccination regimen. Levels of anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies were analyzed at baseline and post-vaccination time points, including 6 weeks post-first dose, and 1 month and 6 months post-second dose. Among naïve participants, the seropositivity rate for anti-S antibodies increased to 96.23% at 1 month after the second dose with anti-S titers peaking at a median of 54.59 U/mL (p < 0.0001). Conversely, COVID-19-recovered participants exhibited significantly elevated anti-S levels after the first dose (median titer: 637.70 U/mL, p < 0.0001), with no notable changes following the second dose. Anti-S levels in both groups declined by 6 months post-second dose. The dynamic pattern of anti-N antibodies was comparable to that of anti-S, albeit with weaker vaccine-induced responses. Notably, levels of both anti-S and anti-N antibodies decreased with advancing age (p < 0.001). Males demonstrated lower anti-N antibody levels compared with females (p = 0.038), while the presence of underlying diseases was associated with higher anti-S antibody levels (p = 0.030). In conclusion, two doses effectively augmented antibody levels in naïve individuals, whereas a single dose may suffice to confer immune protection in COVID-19-recovered individuals. Antibody levels wane over time, necessitating further investigations into the durability of vaccine-mediated immune protection, evidence-based recommendations for preventive vaccination, and the formulation of immunization strategies tailored to distinct populations.