The triglyceride-synthesizing enzyme diacylglycerol acyltransferase 2 modulates the formation of the hepatitis C virus replication organelle.

The replication organelle of hepatitis C virus (HCV), called membranous web, is derived from the endoplasmic reticulum (ER) and mainly comprises double membrane vesicles (DMVs) that concentrate the viral replication complexes. It also tightly associates with lipid droplets (LDs), which are essential for virion morphogenesis. In particular acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a rate-limiting enzyme in triglyceride synthesis, promotes early steps of virus assembly.

Durability of Humoral Responses after an Adapted SARS-CoV-2 mRNA Vaccine Dose in Hemodialysis Patients.

We recently showed that an adapted SARS-CoV-2 vaccine with wildtype and BA.4/BA.5 Omicron subtype epitopes induced a broad short-term immune response in hemodialysis patients.

Pan-serotype dengue virus inhibitor JNJ-A07 targets NS4A-2K-NS4B interaction with NS2B/NS3 and blocks replication organelle formation.

Dengue fever represents a significant medical and socio-economic burden in (sub)tropical regions, yet antivirals for treatment or prophylaxis are lacking. JNJ-A07 was described as highly active against the different genotypes within each serotype of the disease-causing dengue virus (DENV). Based on clustering of resistance mutations it has been assumed to target DENV non-structural protein 4B (NS4B).

Deep mining of the Sequence Read Archive reveals major genetic innovations in coronaviruses and other nidoviruses of aquatic vertebrates.

Virus discovery by genomics and metagenomics empowered studies of viromes, facilitated characterization of pathogen epidemiology, and redefined our understanding of the natural genetic diversity of viruses with profound functional and structural implications. Here we employed a data-driven virus discovery approach that directly queries unprocessed sequencing data in a highly parallelized way and involves a targeted viral genome assembly strategy in a wide range of sequence similarity. By screening more than 269,000 datasets of numerous authors from the Sequence Read Archive and using two metrics that quantitatively assess assembly quality, we discovered 40 nidoviruses from six virus families whose members infect vertebrate hosts.

Phosphatidylinositol 4-Kinase III Alpha Governs Cytoskeletal Organization for Invasiveness of Liver Cancer Cells.

Background & Aims: High expression of phosphatidylinositol 4-kinase III alpha (PI4KIIIα) correlates with poor survival rates in patients with hepatocellular carcinoma. In addition, hepatitis C virus (HCV) infections activate PI4KIIIα and contribute to hepatocellular carcinoma progression. We aimed at mechanistically understanding the impact of PI4KIIIα on the progression of liver cancer and the potential contribution of HCV in this process.

Glycan-directed SARS-CoV-2 inhibition by leek extract and lectins with insights into the mode-of-action of Concanavalin A.

Four years after its outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a global challenge for human health. At its surface, SARS-CoV-2 features numerous extensively glycosylated spike proteins. This glycan coat supports virion docking and entry into host cells and at the same time renders the virus less susceptible to neutralizing antibodies.

Cell-Penetrating Peptide-Bismuth Bicycles.

Cell-penetrating peptides (CPPs) play a significant role in the delivery of cargos into human cells. We report the first CPPs based on peptide-bismuth bicycles, which can be readily obtained from commercially available peptide precursors, making them accessible for a wide range of applications. These CPPs enter human cells as demonstrated by live-cell confocal microscopy using fluorescently labelled peptides.

Live-virus serum neutralization after bivalent SARS-CoV-2 mRNA vaccination in hemodialysis patients.

The development of bivalent booster vaccines addresses the ongoing evolution of the emerging B.1.1.

Zika virus remodelled ER membranes contain proviral factors involved in redox and methylation pathways.

Zika virus (ZIKV) has emerged as a global health issue, yet neither antiviral therapy nor a vaccine are available. ZIKV is an enveloped RNA virus, replicating in the cytoplasm in close association with ER membranes. Here, we isolate ER membranes from ZIKV-infected cells and determine their proteome.

SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle.

Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined.

Viral load of SARS-CoV-2 in surgical smoke in minimally invasive and open surgery: a single-center prospective clinical trial.

At the beginning of the COVID-19 pandemic, it was assumed that SARS-CoV-2 could be transmitted through surgical smoke generated by electrocauterization. Minimally invasive surgery (MIS) was targeted due to potentially higher concentrations of the SARS-CoV-2 particles in the pneumoperitoneum. Some surgical societies even recommended open surgery instead of MIS to prevent the potential spread of SARS-CoV-2 from the pneumoperitoneum.

Identification of host dependency factors involved in SARS-CoV-2 replication organelle formation through proteomics and ultrastructural analysis.

Remodeling of the cellular endomembrane system by viruses allows for efficient and coordinated replication of the viral genome in distinct subcellular compartments termed replication organelles. As a critical step in the viral life cycle, replication organelle formation is an attractive target for therapeutic intervention, but factors central to this process are only partially understood. In this study, we corroborate that two viral proteins, nsp3 and nsp4, are the major drivers of membrane remodeling in SARS-CoV-2 infection.

Quantification of Torque Teno Virus Load to Monitor Short-term Changes in Immunosuppressive Therapy in Kidney Transplant Recipients.

Background: Quantification of torque teno virus (TTV) has been proposed as a surrogate parameter to monitor immunocompetence in kidney transplant recipients (KTRs) early after transplantation. However, its use in monitoring short-term changes of immunosuppression in KTRs late after transplantation requires further investigation.

Methods: In this post hoc analysis, we quantified TTV load in sera of 76 KTRs, with 43 pausing mycophenolic acid (MPA) 1 wk before to 4 wk after COVID-19 vaccination to increase vaccine response.

Dengue virus NS1 secretion is regulated via importin-subunit β1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin.

Dengue virus (DENV) is a major human pathogen that can cause hemorrhagic fever and shock syndrome. One important factor of DENV pathogenicity is non-structural protein 1 (NS1), a glycoprotein that is secreted from infected cells. Here we study the mode of action of the widely used drug ivermectin, used to treat parasitic infections and recently shown to lower NS1 blood levels in DENV-infected patients.

BA.1/BA.5 Immunogenicity, Reactogenicity, and Disease Activity after COVID-19 Vaccination in Patients with ANCA-Associated Vasculitis: A Prospective Observational Cohort Study.

Emerging omicron subtypes with immune escape lead to inadequate vaccine response with breakthrough infections in immunocompromised individuals such as Anti-neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV) patients. As AAV is considered an orphan disease, there are still limited data on SARS-CoV-2 vaccination and prospective studies that have focused exclusively on AAV patients are lacking. In addition, there are safety concerns regarding the use of highly immunogenic mRNA vaccines in autoimmune diseases, and further studies investigating reactogenicity are urgently needed.

Endosomal egress and intercellular transmission of hepatic ApoE-containing lipoproteins and its exploitation by the hepatitis C virus.

Liver-generated plasma Apolipoprotein E (ApoE)-containing lipoproteins (LPs) (ApoE-LPs) play central roles in lipid transport and metabolism. Perturbations of ApoE can result in several metabolic disorders and ApoE genotypes have been associated with multiple diseases. ApoE is synthesized at the endoplasmic reticulum and transported to the Golgi apparatus for LP assembly; however, the ApoE-LPs transport pathway from there to the plasma membrane is largely unknown.

Enhanced SARS-CoV-2 entry via UPR-dependent AMPK-related kinase NUAK2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remodels the endoplasmic reticulum (ER) to form replication organelles, leading to ER stress and unfolded protein response (UPR). However, the role of specific UPR pathways in infection remains unclear. Here, we found that SARS-CoV-2 infection causes marginal activation of signaling sensor IRE1α leading to its phosphorylation, clustering in the form of dense ER-membrane rearrangements with embedded membrane openings, and XBP1 splicing.