The Fatty Acid Lipid Metabolism Nexus in COVID-19.

Enteric symptomology seen in early-stage severe acute respiratory syndrome (SARS)-2003 and COVID-19 is evidence of virus replication occurring in the intestine, liver and pancreas. Aberrant lipid metabolism in morbidly obese individuals adversely affects the COVID-19 immune response and increases disease severity. Such observations are in line with the importance of lipid metabolism in COVID-19, and point to the gut as a site for intervention as well as a therapeutic target in treating the disease.

Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study).

Background: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT).

Genomic-Scale Interaction Involving Complementary Sequences in the Hepatitis C Virus 5'UTR Domain IIa and the RNA-Dependent RNA Polymerase Coding Region Promotes Efficient Virus Replication.

The hepatitis C virus (HCV) genome contains structured elements thought to play important regulatory roles in viral RNA translation and replication processes. We used in vitro RNA binding assays to map interactions involving the HCV 5'UTR and distal sequences in NS5B to examine their impact on viral RNA replication. The data revealed that 5'UTR nucleotides (nt) 95⁻110 in the internal ribosome entry site (IRES) domain IIa and matching nt sequence 8528⁻8543 located in the RNA-dependent RNA polymerase coding region NS5B, form a high-affinity RNA-RNA complex in vitro.

Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture.

Acute Epstein-Barr virus (EBV) infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD). The EBV major virion surface glycoprotein (gp)350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu) version of the murine anti-gp350 neutralizing monoclonal antibody 72a1.

Adaptively introgressed Neandertal haplotype at the OAS locus functionally impacts innate immune responses in humans.

Background: The 2'-5' oligoadenylate synthetase (OAS) locus encodes for three OAS enzymes (OAS1-3) involved in innate immune response. This region harbors high amounts of Neandertal ancestry in non-African populations; yet, strong evidence of positive selection in the OAS region is still lacking.

Results: Here we used a broad array of selection tests in concert with neutral coalescent simulations to demonstrate a signal of adaptive introgression at the OAS locus.

Peptides designed to spatially depict the Epstein-Barr virus major virion glycoprotein gp350 neutralization epitope elicit antibodies that block virus-neutralizing antibody 72A1 interaction with the native gp350 molecule.

Unlabelled: Epstein-Barr virus (EBV) is the etiologic agent of infectious mononucleosis and the root cause of B-cell lymphoproliferative disease in individuals with a weakened immune system, as well as a principal cofactor in nasopharyngeal carcinoma, various lymphomas, and other cancers. The EBV major virion surface glycoprotein gp350 is viewed as the best vaccine candidate to prevent infectious mononucleosis in healthy EBV-naive persons and EBV-related cancers in at-risk individuals. Previous epitope mapping of gp350 revealed only one dominant neutralizing epitope, which has been shown to be the target of the monoclonal antibody 72A1.

Reduction in intracellular HCV RNA and virus protein expression in human hepatoma cells following treatment with 2'-O-methyl-modified anti-core deoxyribozyme.

HCV RNA is gaining greater consideration as a principal target for newer HCV antivirals because its destruction has the potential of eliminating the virus. These newer antivirals include deoxyribozymes (Dz), which are small single-stranded DNA molecules that cleave homologous RNA targets. Using a liver cell model containing functional genomic-length HCV-1b RNA we tested whether 2'-O-methyl-modified Dz, designed to recognize a highly-conserved RNA sequence located within the core-E1 coding region, could recognize and cleave its target sequence in the structural context of a functional HCV RNA molecule.

Oligonucleotide-based therapeutic options against hepatitis C virus infection.

The hepatitis C virus (HCV) is the cause of a silent pandemic that, due to the chronic nature of the disease and the absence of curative therapy, continues to claim an ever-increasing number of lives. Current antiviral regimens have proven largely unsatisfactory for patients with HCV drug-resistant genotypes. It is therefore important to explore alternative therapeutic stratagems whose mode of action allows them to bypass viral resistance.

Designing antibodies for oncology.

The past five years have witnessed the emergence of monoclonal antibodies as important therapeutics for cancer treatment. Lower toxicity for antibodies versus small molecules, the potential for increased efficacy by conjugation to radioisotopes and cellular toxins, or the ability to exploit immune cell functions have led to clinical performances on par or superior to conventional drug therapies. This review outlines the various immunoglobulin design strategies currently available, techniques used to reduce Ig antigenicity and toxicity, and points to consider during the manufacture of antibodies for use in clinical oncology.

Heat shock protein 90 expression in Epstein-Barr virus-infected B cells promotes gammadelta T-cell proliferation in vitro.

The aim of this study was to elucidate the in vitro response of gammadelta T cells to Epstein-Barr virus (EBV)-infected B cells and to determine whether EBV-induced heat shock proteins (HSPs) might serve as gammadelta T-cell stimulants. Cytofluorometric analysis revealed HSP90 cell surface expression in 12% of the EBV-immortalized B-cell population in all four of the B-cell lines tested. HSP27, HSP60, and HSP70 were not detected on the cell surface by cytofluorometry in these same B-cell lines.

Identification, purification and characterization of a novel human blood protein with binding affinity for prostate secretory protein of 94 amino acids.

PSP94 (prostate secretory protein of 94 amino acids), an abundant protein within semen, has reported local functions within the reproductive tract and reported systemic functions. Mechanisms of action remain poorly understood, but binding to undefined molecules within the prostate, pituitary, testis and blood may initiate some of these actions. PSP94 serum measurements, especially of bound and free forms, have potential clinical utility in prostate cancer management.

Nucleosomes activate NF-kappaB in endothelial cells for induction of the proangiogenic cytokine IL-8.

Solid tumors often exhibit regions undergoing apoptosis and necrosis, also referred to as "aponecrosis", juxtaposed to sites of active angiogenesis. We explored whether nucleosomes resulting from aponecrosis induced the angiogenic factor IL-8 in vascular endothelial cells. Results indicate that nucleosomes induced IL-8.

Nucleosomes bind fibroblast growth factor-2 for increased angiogenesis in vitro and in vivo.

Solid tumors often display sites of necrosis near regions of angiogenesis in vivo. As tumor cell necrosis would result in the release of nucleosomes into the extracellular environment, we explored the potential role of nucleosomes in the promotion of angiogenesis. Data indicate that nucleosomes acted similar to heparin and bound to several heparin-binding, proangiogenic factors [i.