Emergence and spread of SARS-CoV-2 lineage B.1.620 with variant of concern-like mutations and deletions.

Distinct SARS-CoV-2 lineages, discovered through various genomic surveillance initiatives, have emerged during the pandemic following unprecedented reductions in worldwide human mobility. We here describe a SARS-CoV-2 lineage - designated B.1.620 - discovered in Lithuania and carrying many mutations and deletions in the spike protein shared with widespread variants of concern (VOCs), including E484K, S477N and deletions HV69Δ, Y144Δ, and LLA241/243Δ. As well as documenting the suite of mutations this lineage carries, we also describe its potential to be resistant to neutralising antibodies, accompanying travel histories for a subset of European cases, evidence of local B.1.620 transmission in Europe with a focus on Lithuania, and significance of its prevalence in Central Africa owing to recent genome sequencing efforts there. We make a case for its likely Central African origin using advanced phylogeographic inference methodologies incorporating recorded travel histories of infected travellers.

Elevated levels of interleukin-33 are associated with allergic and eosinophilic asthma.

IL-33 is a recently discovered cytokine which plays an important role in asthma pathogenesis. AIM: To evaluate serum IL-33 in patients with asthma and healthy controls, and to evaluate the association of IL-33 with different asthma phenotypes. METHODS: Patients with asthma (n = 115) and healthy subjects (n = 85) were included in the study. Subjects with asthma were divided into groups according to their phenotype: allergic/non-allergic, eosinophilic/non-eosinophilic, obese/non-obese and severity according to GINA (mild, moderate and severe). The concentration of IL-33 in serum was measured by standardized enzyme-linked immunosorbent assay. RESULTS: The level of IL-33 was significantly higher in patients with asthma when compared to healthy subjects (672.73 ± 104.47 pg/mL vs 268.52 ± 27.56 pg/mL, P < 0.05). IL-33 was also higher in the allergic asthma group patients when compared to non-allergic asthmatics (844.61 ± 152.08 pg/mL vs 369.56 ± 77.94 pg/mL, P < 0.05). There was a significantly higher serum IL-33 level in the eosinophilic asthma group when compared to the group of non-eosinophilic asthma patients (1001.10 ± 199.11 pg/mL vs 337.49 ± 72.68 pg/mL, P < 0.01). We did not find a significant difference in serum IL-33 level between different asthma severity groups, obese and non-obese asthmatics. CONCLUSION: IL-33 is increased in asthma patients, particularly in some phenotypes: allergic asthma and eosinophilic asthma.

Evaluation of proteasomal gene polymorphisms in Lithuanian patients with asthma.

OBJECTIVE: To investigate polymorphisms of proteasomal genes PSMA6 (rs1048990 and rs2277460), PSMC6 (rs2295826 and rs2295827) and PSMA3 (rs2348071) in Lithuanian patients with asthma. METHODS: One-hundred forty-six asthma patients and 150 control subjects were studied. DNA was extracted from peripheral blood samples. Five single nucleotide polymorphisms (SNP's) of the three proteasomal genes were analyzed using allele-specific amplification or the cleaved amplified polymorphic sequence method. RESULTS: While certain alleles and genotypes of PSMA6 rs2277460 and rs1048990 and PSMA3 rs2348071 SNP's occurred more frequently in asthma patients than in controls, no statistically significant differences in alleles or genotypes of PSMA6, PSMC6 or PSMA3 were observed between asthma patients and control subjects. However, when male and female study subjects were considered separately, we found that the CG genotype of PSMA6 rs1048990 is significantly more frequent in male asthma patients compared to male control subjects. CONCLUSIONS: We found no significant differences in frequencies of selected five proteasomal gene PSMA6, PSMC6 and PSMA3 SNP's between asthma patients and control subjects overall. Among male subjects, however, the CG PSMA6 rs1048990 genotype was significantly more frequent in asthma patients compared with control subjects.

PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity in Latvians, Lithuanians and Taiwanese.

PSMA6 (rs2277460, rs1048990), PSMC6 (rs2295826, rs2295827) and PSMA3 (rs2348071) genetic diversity was investigated in 1438 unrelated subjects from Latvia, Lithuania and Taiwan. In general, polymorphism of each individual locus showed tendencies similar to determined previously in HapMap populations. Main differences concern Taiwanese and include presence of rs2277460 rare allele A not found before in Asians and absence of rs2295827 rare alleles homozygotes TT observed in all other human populations. Observed patterns of SNPs and haplotype diversity were compatible with expectation of neutral model of evolution. Linkage disequilibrium between the rs2295826 and rs2295827 was detected to be complete in Latvians and Lithuanians (D´ = 1; r(2) = 1) and slightly disrupted in Taiwanese (D´ = 0.978; r(2) = 0.901). Population differentiation (FST statistics) was estimated from pairwise population comparisons of loci variability, five locus haplotypes and PSMA6 and PSMC6 two locus haplotypes. Latvians were significantly different from all Asians at each of 5 SNPs and from Lithuanians at the rs1048990 and PSMC6 loci. Lithuanian and Asian populations exhibited similarities at the PSMC6 loci and were different at the PSMA6 and PSMA3 SNPs. Considering five locus haplotypes all European populations were significantly different from Asian; Lithuanian population was different from both Latvian and CEU. Allele specific patterns of transcription factor binding sites and splicing signals were predicted in silico and addressed to eventual functionality of nucleotide substitutions and their potential to be involved in human genome evolution and geographical adaptation. Current study represents a novel step toward a systematic analysis of the proteasomal gene genetic diversity in human populations.

Proteasomes and proteasomal gene polymorphism in association with inflammation and various diseases.

A proteasome, a multicatalytic protein complex, is a central particle of the ubiquitin-proteasome proteolytic pathway in all eukaryotic cells. Through the degradation of most intracellular proteins, proteasomes play a significant role in cell processes, such as cell cycle and division, posttranslational protein quality control, cell signaling, and apoptosis. Therefore, the ubiquitin-proteasome system is necessary to ensure the normal functioning of cells and an organism. The associations between alterations in the ubiquitin-proteasome pathway and the development of various autoimmune, neurodegenerative, inflammatory and other diseases in humans have been established. Moreover, the findings of some studies suggest that proteasomes may participate in the pathogenesis of asthma through the regulation of the nuclear factor kappa B signaling pathway. Recently, much attention has been given to the associations between genes encoding the proteasome and their polymorphism, and various diseases. Associations between some proteasomal genes and myocardial infarction, type 2 diabetes mellitus, and other diseases have already been established. However, the results are inconclusive or conflicting and need further clarification.