Viral immunology最新文献

Numerous studies have highlighted the emergence of coronavirus disease (COVID-19) symptoms reminiscent of Kawasaki disease in children, including fever, heightened multisystem inflammation, and multiorgan involvement, posing a life-threatening complication. Consequently, extensive research endeavors in pediatric have aimed to elucidate the intricate relationship between COVID-19 infection and the immune system. COVID-19 profoundly impacts immune cells, culminating in a cytokine storm that particularly inflicts damage on the pulmonary system. The gravity and vulnerability to COVID-19 are closely intertwined with the vigor of the immune response. In this context, the human leukocyte antigen (HLA) molecule assumes pivotal significance in shaping immune responses. Genetic scrutiny of HLA has unveiled the presence of at least one deleterious allele in children afflicted with multisystem inflammatory syndrome in children (MIS-C). Furthermore, research has demonstrated that COVID-19 exploits the angiotensin-converting enzyme 2 (ACE-2) receptor, transmembrane serine protease type 2, and various other genes to gain entry into host cells, with individuals harboring ACE-2 polymorphisms being at higher risk. Pediatric studies have employed diverse genetic methodologies, such as genome-wide association studies (GWAS) and whole exome sequencing, to scrutinize target genes. These investigations have pinpointed two specific genomic loci linked to the severity and susceptibility of COVID-19, with the HLA locus emerging as a notable risk factor. In this comprehensive review article, we endeavor to assess the available evidence and consolidate data, offering insights into current clinical practices and delineating avenues for future research. Our objective is to advance early diagnosis, stabilization, and appropriate management strategies to mitigate genetic susceptibility's impact on the incidence of COVID-19 in pediatric patients with multisystem inflammation.

Interleukin-36 (IL-36) signaling plays an important role in promoting CD8⁺ T cell-mediated antitumor immune responses. The role of IL-36 signaling in CD8⁺ T cells that are involved in host immune responses during human immunodeficiency virus-1 (HIV-1) infection has not been characterized. Sixty-one patients living with chronic HIV-1 infection and 23 controls were enrolled in this study. The levels of IL-36 cytokine family members were measured by enzyme-linked immunosorbent assay. Purified CD8⁺ T cells were stimulated with recombinant IL-36gamma (1 or 10 ng/mL). The expression of inhibitory receptors, the secretion of cytotoxic molecules and interferon-gamma, and the mRNA levels of apoptosis-related ligands were assessed to evaluate the effect of IL-36gamma on CD8⁺ T cell function in vitro. There were no significant differences in IL-36alpha, IL-36beta, or IL-36 receptor antagonist levels between patients living with chronic HIV-1 infection and controls. Plasma IL-36gamma levels were reduced in patients living with chronic HIV-1 infection. Perforin, granzyme B, and granulysin secretion, as well as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Fas ligand (FasL) mRNA expression, but not programmed death-1 (PD-1) or cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression was downregulated in CD8⁺ T cells from patients living with chronic HIV-1 infection. The addition of both 1 and 10 ng/mL IL-36gamma enhanced perforin, granzyme B, granulysin, and interferon-gamma secretion by CD8⁺ T cells without affecting PD-1/CTLA-4 or TRAIL/FasL mRNA expression in CD8⁺ T cells from patients living with chronic HIV-1 infection. The addition of 1 ng/mL IL-36gamma also promoted perforin and granzyme B secretion by HIV-1-specific CD8⁺ T cells from patients living with chronic HIV-1 infection. The reduced IL-36gamma levels in patients living with chronic HIV-1 infection might be insufficient for the activation of CD8⁺ T cells, leading to CD8⁺ T cell exhaustion.

Human papillomavirus (HPV) infections are common, transmitted by sexual and nonsexual routes. The present case-control setting was designed to examine potential cofactors associated with either persistently low or high HPV-antibody levels. The study subjects were from the Finnish HPV Family cohort of 329 baseline pregnant, non-HPV-vaccinated women, who were sampled for genital and oral HPV-DNA and HPV serology at baseline, and at 12, 24, and 36 months. Antibodies to the L1 major capsid protein of HPV 6, 11, 16, 18, and 45 were analyzed by multiplex HPV serology and HPV genotyping was performed. This study included 59 women, 23 women with persistently low (<200 median fluorescence intensity [MFI]) and 36 women with persistently high and always positive (>200 MFI) levels of these antibodies for all five HPV genotypes. Potential HPV-associated covariates were derived from detailed questionnaires. Only cofactors other than detected HPV genotype significantly impact on the levels of natural HPV antibodies. A higher number of past sexual partners or a history of diagnosed genital warts were significant covariates of high HPV antibody levels (p = 0.023 and p = 0.043, respectively). Of interest, women with a history of allergies presented with low levels of HPV antibodies (p = 0.03), potentially exposing these women to an increased risk of future HPV-related diseases that merit closer surveillance.

Infectious bronchitis virus (IBV), a gammacoronavirus within the Coronaviridae family, is an economically important etiological disease agent in chickens. Both early diagnosis and determination of the immune status of chickens are important for controlling IBV outbreaks in chicken flocks. The N protein is the most abundantly expressed virus-derived protein during IBV infection and can induce a strong immune response by producing antibodies during early infection or immunization. In this study, we found that the amino acid sequences of the N protein between CK/CH/LJL/04I and the other 22 IBVs were conserved, especially in the 1-160 amino acid region. Based on the sequence similarities, the three recombinant proteins, rN160 (amino acid positions 1-160), rN266 (144-409), and rN409 (1-409), were expressed using the Escherichia coli system and subsequently purified. The results demonstrated that the antigenicity and reactivity of rN160 were better than those of rN266 and rN409. As a result, an indirect enzyme-linked immunosorbent assay (ELISA) (rN160 ELISA) was developed to detect the IBV antibody based on the rN160 protein. Using 1,500 clinical field serum samples, the relative sensitivity, specificity, and accuracy of the rN160 ELISA were 98.97%, 92.34%, and 97.93%, respectively, compared to those of a commercial ELISA kit (IDEXX), indicating a strong positive correlation between the two methods. Taken together, these results reveal that the rN160 ELISA is a rapid, simple, and sensitive method for detecting group-specific IBV antibodies for epidemiological investigation and antibody-level monitoring.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.

To better understand how adaptive immune receptors (IRs) in hepatocellular carcinoma (HCC) microenvironments are related to disease outcomes, we employed a chemical complementarity scoring algorithm to quantify electrostatic complementarity between HCC tumor TRB or IGH complementarity-determining region 3 (CDR3) amino acid (AA) sequences and previously characterized hepatitis C virus (HCV) epitopes. High electrostatic complementarity between HCC-resident CDR3s and 12 HCV epitopes was associated with greater survival probabilities, as indicated by two distinct HCC IR CDR3 datasets. Two of the HCV epitopes, HCV*71871 (TRB) and HCV*13458 (IGH), were also determined to represent significantly larger electrostatic CDR3-HCV epitope complementarity in HCV-positive HCC cases, compared with HCV-negative HCC cases, with the CDR3s representing yet a third, independent HCC dataset. Overall, the results indicated the utility of CDR3 AA sequences as biomarkers for HCC patient stratification and as potential guides for the development of therapeutic reagents.

Maternal immunoglobulin G (IgG) antibodies that are passively transferred to newborns through the placenta confer protection if they are exposed to measles virus. A measles outbreak occurred in several European countries including Greece, between 2016 and 2018. A prospective study was conducted in the General Hospital of Lakonia, regarding the measles seropositivity status of mother and newborn pairs. IgG antibody titer for measles was measured in serum samples acquired from pairs of mothers and newborns. The samples were analyzed through quantitative enzyme-linked immunosorbent assay, and antimeasles IgG >200 IU/mL was considered to be protective. Demographic data for mothers and neonates and data regarding immunization status of mothers were analyzed. Study population included 206 mothers and their newborns. In total, 12.6% of mothers (n = 26) and 10.7% of newborns (n = 22) did not have protective serology. A statistically significant positive linear association between maternal and neonatal antibodies was found (rho = 0.924) (p = 0.001). Neonates whose mothers were seropositive had higher antibodies [geometric mean concentration (GMC): 804.8 (728.3-889.2)] than neonates whose mothers were seronegative/borderline [GMC: 97.7 (64.2-148.8)] (p = 0.001). In the study area, a significant rate of mothers and newborns was found to have nonprotective measles serology that exceeds the limit required for herd immunity. Vaccination coverage in women of reproductive age should be increased to reduce potential for future measles epidemics.