MicroRNA Expression Patterns of CD8+ T Cells in Acute and Chronic Brucellosis.

Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis

miRNAs with 2^(-Avg.(Delta(Ct)) values were evaluated between A. Acute-Control, B. Acute-Chronic C. Chronic-Control patients depend on miRNA microarray analysis (p< 0.05, cut off = 2).

<p>The volcano plot demonstrates the differential expression of the illustrated miRNAs; dots in light represent miRNAs that did not achieve significant changes in expression, dots in dark on the left indicate the miRNAswith significantly downregulated expression and dots in dark on the right indicate the miRNAswith significantly upregulated expression.</p

Target gene prediction for the 2 down regulated miRNAs, miR-126-5p and miR-4753-3p depend on KEGG analysis.

<p>Target gene prediction for the 2 down regulated miRNAs, miR-126-5p and miR-4753-3p depend on KEGG analysis.</p

Altered miRNA expressions in acute brucellosis.

<p>Altered miRNA expressions in acute brucellosis.</p

Pathway Analysis of miR-4753-3p according to KEGG function annotations.

<p>Pathway Analysis of miR-4753-3p according to KEGG function annotations.</p

Altered miRNA expressions in chronic brucellosis.

<p>Altered miRNA expressions in chronic brucellosis.</p

Significantly altered miRNA expressions in both chronic and acute brucellosis cases in compare to control group.

<p>Significantly altered miRNA expressions in both chronic and acute brucellosis cases in compare to control group.</p

Pathway Analysis of 2 down regulated miRNAs, miR-126-5p and miR-4753-3p according to KEGG function annotations.

<p>Pathway Analysis of 2 down regulated miRNAs, miR-126-5p and miR-4753-3p according to KEGG function annotations.</p

Pathway Analysis of miR-126-5p according to KEGG function annotations.

<p>Pathway Analysis of miR-126-5p according to KEGG function annotations.</p

Multivalency transforms SARS-CoV-2 antibodies into broad and ultrapotent neutralizers

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes Coronavirus Disease 2019 (COVID-19), has caused a global pandemic. Antibodies are powerful biotherapeutics to fight viral infections; however, discovery of the most potent and broadly acting clones can be lengthy. Here, we used the human apoferritin protomer as a modular subunit to drive oligomerization of antibody fragments and transform antibodies targeting SARS-CoV-2 into exceptionally potent neutralizers. Using this platform, half-maximal inhibitory concentration (IC50) values as low as 9 × 10−14 M were achieved as a result of up to 10,000-fold potency enhancements. Combination of three different antibody specificities and the fragment crystallizable (Fc) domain on a single multivalent molecule conferred the ability to overcome viral sequence variability together with outstanding potency and Ig-like in vivo bioavailability. This MULTi-specific, multi-Affinity antiBODY (Multabody; or MB) platform contributes a new class of medical countermeasures against COVID-19 and an efficient approach to rapidly deploy potent and broadly-acting therapeutics against infectious diseases of global health importance.N