Development of accelerated high-throughput antiviral screening systems for emerging orthomyxoviruses.

Bourbon virus (BRBV) is an emerging tick-borne orthomyxovirus that causes severe febrile illness in humans. There are no specific treatments for BRBV disease currently available. Here, we developed a highly accessible and robust, quantitative fluorescence-based BRBV minigenome (MG) system and applied it to high-throughput antiviral drug screening.

Inactivation of replication-competent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on common surfaces by disinfectants.

This experimental laboratory-based study evaluated two disinfectants' efficacy against replication-competent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on three surfaces. Disinfectants were effictive at eliminating the presence, viability, and subsequent replication of SARS-CoV-2 on all surfaces. Although SARS-CoV-2 likely spreads primarily via airborne transmission, layered mitigation should include high-touch surface disinfection.

Attacking COVID-19 Progression Using Multi-Drug Therapy for Synergetic Target Engagement.

COVID-19 is a devastating respiratory and inflammatory illness caused by a new coronavirus that is rapidly spreading throughout the human population. Over the past 12 months, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has already infected over 160 million (>20% located in United States) and killed more than 3.3 million people around the world (>20% deaths in USA).

The NF-κB inhibitor, SC75741, is a novel antiviral against emerging tick-borne bandaviruses.

Severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV) cause viral hemorrhagic fever-like illnesses in humans due to an aberrant host inflammatory response, which contributes to pathogenesis. Here, we established two separate minigenome (MG) systems based on the M-segment of SFTSV and HRTV. Following characterization of both systems for SFTSV and HRTV, we used them as a platform to screen potential compounds that inhibit viral RNA synthesis.

Hepatocytes lacking thioredoxin reductase 1 have normal replicative potential during development and regeneration.

Cells require ribonucleotide reductase (RNR) activity for DNA replication. In bacteria, electrons can flow from NADPH to RNR by either a thioredoxin-reductase- or a glutathione-reductase-dependent route. Yeast and plants artificially lacking thioredoxin reductases exhibit a slow-growth phenotype, suggesting glutathione-reductase-dependent routes are poor at supporting DNA replication in these organisms.

ICP0 antagonizes ICP4-dependent silencing of the herpes simplex virus ICP0 gene.

ICP0 is a regulatory protein that plays a critical role in the replication-latency balance of herpes simplex virus (HSV). Absence of ICP0 renders HSV prone to establish quiescent infections, and thus cellular repressor(s) are believed to silence HSV mRNA synthesis when ICP0 fails to accumulate. To date, an ICP0-antagonized repressor has not been identified that restricts HSV mRNA synthesis by more than 2-fold.

Cre activity in fetal albCre mouse hepatocytes: Utility for developmental studies.

The albCre transgene, having Cre recombinase driven by the serum albumin (alb) gene promoter, is commonly used to generate adult mice having reliable hepatocyte-specific recombination of loxP-flanked ("floxed") alleles. Based on previous studies, it has been unclear whether albCre transgenes are also reliable in fetal and juvenile mice. Perinatal liver undergoes a dynamic transition from being predominantly hematopoietic to predominantly hepatic.

Cytoprotective Nrf2 pathway is induced in chronically txnrd 1-deficient hepatocytes.

Background: Metabolically active cells require robust mechanisms to combat oxidative stress. The cytoplasmic thioredoxin reductase/thioredoxin (Txnrd1/Txn1) system maintains reduced protein dithiols and provides electrons to some cellular reductases, including peroxiredoxins.

Principal Findings: Here we generated mice in which the txnrd1 gene, encoding Txnrd1, was specifically disrupted in all parenchymal hepatocytes.

Translational regulation of rotavirus gene expression.

Rotavirus mRNAs are transcribed from 11 genomic dsRNA segments within a subviral particle. The mRNAs are extruded into the cytoplasm where they serve as mRNA for protein synthesis and as templates for packaging and replication into dsRNA. The molecular steps in the replication pathway that regulate the levels of viral gene expression are not well defined.

Interferon regulatory factor 3 is a cellular partner of rotavirus NSP1.

The rotavirus nonstructural protein NSP1 is the least conserved protein in the rotavirus genome, and its function in the replication cycle is not known. We employed NSP1 as bait in the yeast two-hybrid interaction trap to identify candidate cellular partners of NSP1 that may provide clues to its function. Interferon regulatory factor 3 (IRF-3) was identified as an NSP1 interactor.