Viral immunology最新文献

This study aims to evaluate the estimate of causal relationship between Epstein-Barr virus (EBV) antibody levels and autoimmune diseases (AIDs), such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), through bidirectional two-sample Mendelian randomization (MR) analysis. Despite 50 years of research into the link between EBV infection and AIDs, inconsistent results persist due to the complex mechanisms of EBV within the body. We utilized large-scale genome-wide association studies (GWAS) data from the Integrative Epidemiology Unit (IEU) Open GWAS Project database to conduct rigorous MR analysis, incorporating various sensitivity analyses to assess potential impacts and ensure robustness. EBV antibodies (including VCA-IgG, ZEBRA-IgG, EBNA-1-IgG, and EA-D-IgG) were used as exposure variables, whereas RA and SLE served as outcome variables. In the reverse analysis, RA and SLE were treated as exposure variables and EBV antibodies as outcome variables. When EBV antibodies are designated as the exposure variables, the random-effects inverse-variance weighted (IVW) analysis indicated a significant negative genetic causal relationship between EBV EA-D antibody levels and RA (p = 0.007, odds ratio [OR] = 0.700, 95% confidence interval [CI] = [0.539-0.907]). No significant genetic causal relationship was found between SLE and EBV antibody levels. When RA and SLE are designated as the exposure variables, the random-effects IVW analysis revealed significant positive genetic causal relationships between SLE and EBV ZEBRA antibody levels (p = 0.009, OR = 1.028, 95% CI = [1.007-1.050]) and EBV EA-D antibody levels (p = 0.005, OR = 1.032, 95% CI = [1.009-1.054]). No significant genetic causal relationship was observed between RA and EBV antibody levels. This study offers compelling evidence of a causal relationship between EBV antibody levels and AIDs through MR analysis. Our findings lay a new foundation and perspective for future research directions, clinical prognosis, and treatment.

Field evidence indicates differences in the rate and severity of COVID-19 infection among Afghans and Iranians, potentially influenced by individual genomic variances. Therefore, investigating the potential causes of these disparities holds significant clinical importance. This study aims to explore and compare variations in the genes encoding angiotensin-converting enzyme 1 (ACE1) and angiotensin-converting enzyme 2 (ACE2), along with total ACE activity levels in the blood of Afghans and Iranians with COVID-19, to assess any potential correlation with disease severity. In this case-control study, 124 Afghans and 124 Iranians with COVID-19 residing in Rafsanjan city, Iran, were examined. Blood samples were collected from all subjects, and serum was isolated for measuring total ACE activity using the kinetic method. DNA extraction was performed using the salting-out method, and gene polymorphisms of ACE1 and ACE2 were determined through polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism techniques. The DD genotype and D allele, as well as the GG genotype and G allele, were more prevalent among individuals with severe COVID-19 cases compared with those with mild symptoms, indicating an increased risk of severe infection. Although the Iranian group exhibited higher levels of these genetic components, along with longer hospital stays, intensive care unit admissions, and mortality rates than the Afghan group, the differences were not statistically significant. Furthermore, individuals with the DD genotype displayed double the total ACE activity levels compared with those with the II genotype, with the ID genotype falling in between. The presence of the DD genotype and D allele, as well as the GG genotype and G allele, likely serves as a significant risk factor for COVID-19 susceptibility, potentially heightening the risk of severe infection among Iranians compared with Afghans.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and first identified in Wuhan, China, in December 2019, has led to global efforts in vaccination to mitigate rising morbidity and mortality, with vaccines proving crucial in controlling the pandemic. This study evaluated the humoral responses to the inactivated virus vaccine Sinopharm or Koxing Kerlafor, the protein subunit vaccine ZF001, and the adenoviral vector vaccine Convidecia after 18 months of inactivated virus vaccination by heterologous and homologous booster vaccination in patients with previous SARS-CoV-2 infection and healthy individuals. We discovered that patients who had recovered from the infection and then received a third vaccine dose (booster) exhibited durable immunity. Furthermore, the heterologous booster vaccine induced higher neutralizing antibody responses compared with the homologous booster. These findings offer valuable insights into the efficacy of different COVID-19 vaccine strategies following booster immunization.

This study investigates the demographic, clinical characteristics, virological profiles, and immunological responses of patients with viral encephalitis (VE) compared with a control group. The VE group displayed a wide range of neurological symptoms. Virological analysis revealed the predominance of Herpesviridae family viruses. Immune responses in cerebrospinal fluid (CSF) from patients with VE were examined, highlighting an immunological shift toward T helper 1 (Th1) cells dominance, altered T helper 17 cells/regulatory T cells (Th17/Tregs) balance, and high interleukin-6 expression. These findings provide insights into the complex immunological landscape of VE, highlighting the role of specific cytokines and T cell subsets in its pathogenesis and potentially guiding targeted therapeutic strategies.

This study aims to explore the mechanism underlying the role of ubiquitin-specific protease 14 (USP14) in regulating P53 expression and influencing the development of hepatitis B. The animal and cell models of hepatitis B were constructed. The mRNA and protein expression of USP14, mouse double minute 2 (MDM2), and P53 were detected by western blot and qPCR. The USP14 overexpression vector was constructed. The pathological changes of liver tissue were detected by HE and Masson staining. Protein immunoprecipitation was used to detect the interaction between MDM2 and P53, as well as between MDM2 and USP14. The ubiquitination levels of P53 after USP14 overexpression were detected. qPCR and western blot were used to detect the expression of MDM2, Bcl-2, P53, Bax, and Caspase-1 in vivo and in vitro. Compared with the control group, the model group showed increased cell proliferation, increased expression of MDM2 and Bcl-2 in cells and liver tissue, and decreased expression of P53, Bax, and Caspase-1. Compared with the model group, overexpression of USP14 resulted in a decrease in MDM2 expression and an increase in P53 expression. After transfection with the USP14 overexpression plasmid, cell proliferation was inhibited, and the expression of MDM2 and Bcl-2 was decreased in cells and liver tissue, while the expression of P53, Bax, and Caspase-1 was increased. In the model of hepatitis B, USP14 upregulation downregulated MDM2 and promoted P53 deubiquitination to delay the invasion of hepatitis B virus and the development of hepatitis.

Following viral infection, antigen-restricted T lymphocytes are activated and recognize infected cells to eliminate them. A subset of T cells differentiates into memory lymphocytes able to counteract viral rechallenge in a faster and enhanced way. SARS-CoV-2 can escape immune responses leading to a poor clinical outcome. Immune escape can be associated with the failure of the development of T cell memory compartments. The aim of this study is to characterize the T memory subsets and to test the immune response against class I- and II-restricted immunodominant epitopes shared by ancestral and SARS-CoV-2 variants strains. T memory subsets and recognition of SARS-CoV-2S Spike-specific epitopes were analyzed by flow cytometry on 14 fully vaccinated healthy donors (HDV) and 18 COVID-19 recovered patients (CD). The results obtained showed that CD8+ T naïve subset numbers decreased in association with a significant increase of the effector memory T cell subset whereas there was a small increase in the percentage of SARS-CoV-2 antigen-restricted T clones in both CD4⁺ and CD8+ subset in the CD compared to HDV sample. Collectively, these features may reflect a broader cytotoxic T cell repertoire stimulated by the virus during the natural infection compared to the spike-restricted response activated during vaccination.

Viral infections are one of the principal causes of global primary health crises, with increased rate of infection and mortality demonstrated by the newer progeny of viruses. Viral invasion of the host involves utilization of various cellular machinery. Ubiquitination is one of a few central regulatory systems used by viruses for establishment of the infections in the host. Members of the ubiquitination system are involved in carrying out proteasomal degradation or functional modification of proteins in numerous cellular processes. E3 ubiquitin ligases play a major role in this system through recognition and recruitment of protein substrates and catalyzing the transfer of ubiquitin to these substrates. The versatility of ubiquitin ligases frequently makes them useful tools for the viruses, for either utilizing or degrading other cellular machineries, for carrying out their multiplication or inactivating the defensive strategies of the host. Therefore, these ligases are important targets for aiming at major pathways causing viral protein degradation or functional modification of the infection process. In this review, we have discussed the role and mechanism of different types of ubiquitin ligases in the context of infections of mainly human viruses, highlighting the viral proteins directly interacting with the ligases. Knowledge about these direct interactions is central in understanding the ubiquitin-dependent processes. This comprehensive account may also be beneficial for pharmaceutical exploration of E3 ligase-based broad-spectrum antiviral treatment.

Human T-cell lymphotropic virus type-I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the main neurological manifestation of HTLV-I, is a chronic inflammatory disease. Viral-host interaction and host genetics are two important contributors to the development of the HAM/TSP. This study was conducted to measure the serum level of tumor necrosis factor-alpha-like weak inducer of apoptosis (TWEAK) by ELISA method in three groups of participants including 34 HAM/TSP patients (HAM/TSP), 35 asymptomatic HTLV-1 carriers (ACs), and 20 healthy controls (HCs). Also, the titer of the proviral load in two groups of HAM/TSP and ACs was assessed by the real-time polymerase chain reaction (PCR). The statistical results showed that, there is no significant difference between the three groups in TWEAK cytokine level (p = 0.667). Also, there was no significant difference in proviral load titer between groups of HAM/TSP and ACs (p = 0.08). Furthermore, no significant difference was observed between proviral load and TWEAK cytokine concentration between groups of HAM/TSP and ACs. Our findings showed that despite the inflammatory nature of HAM/TSP disease, the expression level of TWEAK in HAM/TSP patients is not significantly different from the groups of ACs and HCs. Therefore, the involvement of other factors in causing HAM/TSP is not unexpected.

Vaccines have always been a critical tool in preventing infectious diseases. However, the development of traditional vaccines often takes a long time and may struggle to address the challenge of rapidly mutating viruses. The emergence of mRNA technology has brought revolutionary changes to vaccine development, particularly in rapidly responding to the threat of emerging viruses. The global promotion of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 has demonstrated the importance of mRNA technology. Also, mRNA vaccines targeting viruses such as influenza, respiratory syncytial virus, and Ebola are under development. These vaccines have shown promising preventive effects and safety profiles in clinical trials, although the duration of immune protection is still under evaluation. However, the development of mRNA vaccines also faces many challenges, such as stability, efficacy, and individual differences in immune response. Researchers adopt various strategies to address these challenges. Anyway, mRNA vaccines have shown enormous potential in combating viral diseases. With further development and technological maturity, mRNA vaccines are expected to have a profound impact on public health and vaccine equity. This review discussed the potential of mRNA vaccines to fight against viruses, current progress in clinical trials, challenges faced, and future prospects, providing a comprehensive scientific basis and reference for future research.

The plausible effects of SARS-CoV-2 infection on the expression of anti/proapoptotic molecules have been suspected. This cohort study examined the expression of p53, Bcl-2, Bid, Bak, and Bax molecules, the genes associated with induction or inhibition of apoptosis, in the SARS-CoV-2-infected patients with severe and mild symptoms in an Iranian population. In this 6-month cohort study, the expression of p53, Bcl-2, Bid, Bak, and Bax molecules was evaluated at onset of diagnosis, 24 h after symptom onset, and 6 months later in the nasopharyngeal cells of SARS-CoV-2-infected hospitalized patients and outpatients in comparison with healthy controls using the real-time PCR technique. At the onset of the study, the relative expression of p53, Bcl-2, Bid, Bak, and Bax significantly increased in the SARS-CoV-2-infected hospitalized patients and decreased after 6 months. The healthy controls showed potential positive correlations among the molecules, but the patients did not show these correlations. Since SARS-CoV-2 needs host cell survival, it appears that the virus induces the expression of Bcl-2 as an antiapoptotic molecule, and the host cells upregulate the proapoptotic molecules to neutralize the effects. Dysregulation of correlation expression of the molecules among the patients proved that SARS-CoV-2 affects the expression of the molecules involved in apoptosis. SARS-CoV-2 could be considered an important factor that regulates the expression of several molecules participating in cancer pathogenesis.