Viral immunology最新文献

Background and aims: Chronic hepatitis B (CHB) drives liver fibrosis, contributing to chronic liver disease. Galectin-3 (Gal-3), a lectin linked to inflammation and fibrosis, was investigated for its association with liver injury severity in HBeAg-negative CHB and chronic hepatitis B virus (HBV) infection (CHI) patients. Methods: We enrolled 25 CHB, 25 CHI, and 25 healthy controls. Serum Gal-3 levels were measured in all subjects, with liver biopsies performed in CHB patients. Gal-3 and HBV DNA levels were monitored at 0, 1, 3, 6, and 12 months during antiviral therapy in CHB patients. Results: Serum Gal-3 levels were significantly higher in CHI (median: 422 U/L, interquartile range [IQR]: 144-900) and CHB (median: 567 U/L, IQR: 196-1093) patients than controls (median: 179 U/L, IQR: 79-350; p < 0.001). Although Gal-3 levels were higher in CHB than CHI, the difference was not significant (p = 0.08). Median Gal-3 levels in CHB patients decreased from 567 U/L to 288 U/L after 12 months of antiviral therapy (p = 0.043 after excluding an outlier). Gal-3 levels showed weak correlations with HBV DNA (Spearman's rho = 0.32, p = 0.12), ALT (rho = 0.28, p = 0.17), and fibrosis scores (rho = 0.35, p = 0.09). Conclusions: Elevated Gal-3 levels correlate with HBeAg-negative CHB and CHI, with a significant decline posttreatment in CHB. If validated, Gal-3 could serve as a noninvasive marker for fibrosis and treatment response.

This study aimed to generate a monoclonal antibody (mAb) against feline coronavirus (FCoV) spike (S) protein and to develop a colloidal gold immunochromatographic strip for the rapid and accurate FCoV detection. BALB/c mice were immunized with the purified protein, and hybridoma technology was employed to produce highly effective mAb. A positive hybridoma cell line (E5) was identified, which stably secreted mAb with a high titer of 1:256000 against the FCoV S recombinant protein. Western blot analysis confirmed the mAb E5's specificity. The established test strip can detect FCoV specifically and detect the antigen concentrations as low as 1.2 × 10^-7 mg/mL. The diagnostic sensitivity and specificity of the FCoV detection strip for feline coronavirus infections were 94.2% and 100%, respectively, as confirmed by reverse transcription polymerase chain reaction (RT-PCR). The detection strip demonstrated no cross-reactivity with other feline pathogens and showed consistent results in reproducibility tests. The developed colloidal gold test strip offers a highly sensitive and specific tool for rapid FCoV detection, contributing to improved real-time epidemic monitoring.

Following reports of highly pathogenic avian influenza H5N1 infections of dairy cattle in the United States in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the United States has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

SARS-CoV-2 has evolved into several variants of concern, with Omicron and its subvariants currently being the most prevalent. Previously, we developed a mouse monoclonal antibody (m1E3H12 mAb) specific to the receptor binding domain of SARS-CoV-2 Omicron spike protein, and the mAb showed neutralizing activity against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB. Here, we showed that the mAb provided protection against SARS-CoV-2 Omicron infection in K18-hACE2 transgenic mice when administered intranasally. The mAb treatment reduced viral loads in both the brain and lungs. Additionally, the elevated levels of RANTES (CCL5) and MIP-3 alpha (CCL20) in the brain following SARS-CoV-2 Omicron infection showed a decreasing trend after mAb treatment. Therefore, we conclude that our mAb specific to SARS-CoV-2 Omicron spike protein has the potential to be applied as therapeutics against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB.

BK virus is a childhood virus that can reactivate in immunocompromised individuals, particularly organ transplant recipients, causing transplant rejection due to BK virus-associated nephropathy. The study aimed to assess the prevalence of BK virus infection in kidney transplant recipients, examine the relationship between demographic and laboratory factors and active infection, evaluate the impact of reducing immunosuppressive drug doses on BK virus reactivation, and explore the genotyping of BK virus strains in this population. This cross-sectional study utilized 245 serum samples from kidney transplant recipients. Viral DNA was extracted from these samples, and initially, Nested PCR was employed for screening to ensure accuracy, with primers targeting a segment of the VP1 gene used to detect the BK virus genome. Real-Time PCR was subsequently performed on positive samples to measure viral load more precisely. The prevalence of BK virus infection among kidney transplant recipients was 5.3%. Out of 245 kidney transplant recipients, 13 individuals were diagnosed with active BK virus infection. Genotype I was the most prevalent, accounting for 90% of the cases. The relationship between demographic factors (gender and age) and laboratory parameters (fasting blood glucose, creatinine, hemoglobin, and platelet count) was examined in both kidney transplant recipients with and without active BK virus infection. The results revealed that a reduction in immunosuppressive drug dosages, particularly tacrolimus, was associated with a decrease in BK viral load, potentially contributing to a lower incidence of active BK virus infections. Additionally, hematological analysis showed a significant decrease in hemoglobin levels in kidney transplant recipients with active BK virus infection, accompanied by a significant increase in serum creatinine levels. Balancing immunosuppressive therapy, especially reducing tacrolimus, helps control BK virus reactivation and preserve graft function. Regular monitoring of hematological parameters and viral load is crucial for optimal management in kidney transplant recipients.

Cell senescence, induced by various internal and external stresses, plays a significant role in the development of various diseases such as cancer, neurodegeneration, and infections. Viral infections can also induce cellular senescence, known as virus-induced senescence (VIS), which occurs in close correlation with the severity of the viral infections. However, due to the unclear mechanisms underlying VIS, the effective inhibition of VIS during viral infections is challenging, leading to rapid disease progression. This study utilized the widely used vesicular stomatitis virus (VSV) model virus to simulate RNA virus infections for exploring the mechanisms by which RNA viruses induce cellular senescence. The results indicated that VSV infection, both in vitro and in vivo, could significantly induce the upregulation of senescence-associated markers and the secretion of the senescence-associated secretory phenotype (SASP), promoting the senescence process. Further research found that the activation of the NF-κB pathway played a crucial role in VSV-induced cellular senescence. Targeted inhibition of the NF-κB pathway could reduce the level of organ senescence induced by viral infections, decrease the expression of SASP inflammatory factors, and ameliorate tissue damage in mice. Overall, our findings reveal the mechanisms underlying RNA virus-associated VIS and provide potential targets for inhibiting the occurrence of VIS and preventing disease progression.

The aim of this study was to compare immune response against SARS-CoV-2 in Balb/C mice when self-amplifying RNA lipid nanoparticles (saRNA LNPs) combined with TLR4 Agonist (monophosphoryl lipid A) as the adjuvant 1 and TLR9 Agonist (CpG) as the adjuvant 2. Here, we found that the size distribution of saRNA LNPs was 88-165 nm with a mean size of 126 nm. Although TLR4 Agonist (adjuvant 1) and TLR9 Agonist (adjuvant 2) could increase the expression of S-protein in HEK293T/17 cells compared with saRNA LNPs alone, the combination of both adjuvants had a significant effect on the expression of the S-protein. Moreover, combining TLR4 Agonist (adjuvant 1) and TLR9 Agonist (adjuvant 2) increased the antibody (IgG and IgA) titer. Here, the ratio of IgG2a/IgG1 showed a T helper type 1-biased response. ELISpot test showed the mice vaccinated with saRNA LNPs+ TLR4 Agonist and TLR9 Agonist had significantly more secreting cells compared with other vaccinated mice (p < 0.05). The secretion of interleukin (IL)-4 and interferons (IFN)-γ by re-stimulated splenocytes confirmed these data. Significant differences in concentration of IL-4 and IFN-γ produced by activated splenocytes were also seen in the mice vaccinated with saRNA LNPs+ TLR4 Agonist and microparticles compared with other groups (p < 0.05). The highest quantity of S-protein was detected in the blood, followed by the small intestine and spleen. The interesting thing was that no significant difference was seen between the amount of S-protein induced by different formulations and the type of adjuvant did not affect the biodistribution.

Analysis of the viral load in respiratory syncytial virus (RSV) infection has focused on the nasopharyngeal site (NPS) near the lower respiratory tract, which is the primary lesion site, and the viral load in the anterior nasal site (ANS) near the nostrils has not been clarified in adults or children. The study evaluated the nasal distribution of RSV. A total of 49 patients, with 0 months to 71 years of age, participated in the study. A total of 774 specimens were collected from the ANS and NPS. In the pediatric group, the highest viral load in the NPS was 1.1 × 10¹⁰ copies/mL on day 1 of onset, and the highest in the ANS was 4.1 × 10⁹ copies/mL on day 2. Thereafter, the viral load at both sites decreased gradually over time. The adult group showed a peak viral load on the onset day, with 1.5 × 10¹⁰ copies/mL in the NPS and 8.4 × 10⁹ copies/mL in the ANS. By day 7 of onset, the viral load was 3.9 × 10⁸ copies/mL in the NPS and 1.3 × 10⁸ copies/mL in the ANS, indicating that the viral load at both sites remained parallel. We demonstrated that the RSV load was present in the ANS and NPS of children and adults from the date of onset. The ANS is closer to the nostrils and is a more promising specimen collection site than the NPS at all ages but has a lower viral load than the NPS.

Human metapneumovirus (HMPV) is a prominent respiratory pathogen causing significant morbidity and mortality worldwide, mostly in young teenagers, the old, and immunocompromised individuals. Despite its clinical impact, no licensed vaccine is currently available, highlighting the urgent need for effective prophylactic strategies. This research aimed to design a multiepitope vaccine (MEV) targeting conserved and immunodominant regions of HMPV, leveraging immunoinformatics tools to ensure broad coverage and efficacy against the virus and its diverse sublineages. Glycoproteins from HMPV genotypes A2a, A2b, and A2c were analyzed to identify 18 highly antigenic and overlapping epitopes capable of eliciting robust B-cell, T-cell, and interferon-gamma (IFN-γ)-mediated immune responses. Toxicity and allergenicity studies confirmed the safety of particular epitopes, which were incorporated into two vaccine constructs using immunogenic linkers and adjuvants. The chimeric vaccines displayed high antigenicity, molecular stability, and nonallergenic properties. Structural refinement and Ramachandran plot analyses established the stability and accuracy of the 3D models. Molecular docking studies verified strong interactions with immune receptors, particularly toll-like receptor (TLR)2, TLR3, TLR4, TLR8, and human leukocyte antigen molecules, indicating robust immune stimulation potential. Molecular dynamics simulations further validated the vaccine's stability and interaction dynamics, with immune simulations predicting promising responses. The designed vaccine constructs were shown to be highly soluble, stable, and suitable for recombinant expression in Escherichia coli, enabling further biochemical and immunoreactivity validation. These findings provide a foundation for next-generation vaccine development against HMPV, offering promising avenues for clinical application and future research. [Figure: see text].

Varicella Zoster Virus (VZV), a member of the herpes virus family, causes varicella (chicken pox) upon primary infection and later manifests as herpes zoster ([HZ] or shingles) upon reactivation. VZV-specific T-cell immunity acquired during primary infection aids recovery, with the virus lying latent in neuronal ganglia until it transports to the skin axonally during reactivation. It has been well-established that reduced T-cell recognition and proliferation, as well as immunosuppression more generally, contribute to VZV reactivation. It has also been discovered that seasonal variation, which is linked to ultraviolet radiation (UVR), correlates with increased HZ cases. This correlation may be explained by the direct immunosuppressant effects of UVR, with melanin offering photoprotective effects that decrease reactivation rates. However, an underexplored aspect of this correlation is the potential role of the skin microbiome in UVR-induced VZV reactivation. Vital for skin homeostasis and immune modulation, the skin microbiome has been found to influence various skin conditions. Preliminary evidence suggests that microbiome diversity may influence VZV reactivation rates, supported by antibiotic-induced effects on HZ incidence. Research also indicates the microbiome's modulating effect on UVR-induced immune suppression, emphasizing its potential significance in VZV reactivation. The skin microbiome's contribution may also help further explain sex and ethnicity-specific variations in VZV reactivation rates. Understanding the interplay between UVR, the skin microbiome, and VZV reactivation warrants further investigation and may help uncover preventive strategies for mitigating VZV reactivation.