Vaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction.

The molecular mechanisms by which vaccinia virus (VACV), the prototypical member of the poxviridae family, reprograms host cell metabolism remain largely unexplored. Additionally, cells sense and respond to fluctuating nutrient availability, thereby modulating metabolic pathways to ensure cellular homeostasis. Understanding how VACV modulates metabolic pathways in response to nutrient signals is crucial for understanding viral replication mechanisms, with the potential for developing antiviral therapies.

Sample Preparation for Global Metabolic Profiling of Vaccinia Virus-Infected Primary Human Foreskin Fibroblasts.

Vaccinia virus (VACV), the prototype member of the Poxviridae family, has played a crucial role in medicine as a key component in the development of smallpox vaccines, contributing to the eradication of this deadly disease. Beyond its historical significance, VACV continues to be pivotal in researching metabolic alterations induced by viral infections. Studies have revealed that VACV can impact pathways such as glycolysis, the tricarboxylic acid (TCA) cycle, and lipid metabolism in host cells, offering valuable insights into host-virus interactions and broader cellular metabolism.

Stimulation of neutral lipid synthesis via viral growth factor signaling and ATP citrate lyase during vaccinia virus infection.

Fatty acid metabolism can provide various products essential for viral infections. How vaccinia virus (VACV), the prototype of poxviruses, modulates fatty acid metabolism is not well understood. Here, we show that VACV infection results in increased neutral lipid droplet synthesis, the organelles that play a crucial role in storing and mobilizing fatty acids for energy production via β-oxidation.

Role of vaccinia virus growth factor in stimulating the mTORC1-CAD axis of the pyrimidine pathway under different nutritional cues.

Vaccinia virus (VACV), the prototype poxvirus, actively reprograms host cell metabolism upon infection. However, the nature and molecular mechanisms remain largely elusive. Given the diverse nutritional exposures of cells in different physiological contexts, it is essential to understand how VACV may alter various metabolic pathways in different nutritional conditions.

Nrf2 regulates the activation-driven expansion of CD4 T-cells by differentially modulating glucose and glutamine metabolism.

Upon antigenic stimulation, CD4 T-cells undergo clonal expansion, elevating their bioenergetic demands and utilization of nutrients like glucose and glutamine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a well-known regulator of oxidative stress, but its involvement in modulating the metabolism of CD4 T-cells remains unexplored. Here, we elucidate the role of Nrf2 beyond the traditional antioxidation, in modulating activation-driven expansion of CD4 T-cells by influencing their nutrient metabolism.

Antiviral activities of two nucleos(t)ide analogs against vaccinia, mpox, and cowpox viruses in primary human fibroblasts.

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox (formerly monkeypox). Identifying novel and potent antiviral compounds is critical to successful drug development targeting poxviruses. Here we tested two compounds, nucleoside trifluridine, and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV), mpox virus (MPXV), and cowpox virus (CPXV) in physiologically relevant primary human fibroblasts.

Beyond Antioxidation: Keap1-Nrf2 in the Development and Effector Functions of Adaptive Immune Cells.

Ubiquitously expressed in mammalian cells, the Kelch-like ECH-associated protein 1 (Keap1)-NF erythroid 2-related factor 2 (Nrf2) complex forms the evolutionarily conserved antioxidation system to tackle oxidative stress caused by reactive oxygen species. Reactive oxygen species, generated as byproducts of cellular metabolism, were identified as essential second messengers for T cell signaling, activation, and effector responses. Apart from its traditional role as an antioxidant, a growing body of evidence indicates that Nrf2, tightly regulated by Keap1, modulates immune responses and regulates cellular metabolism.

Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts.

Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts.

Inhibitors of One or More Cellular Aurora Kinases Impair the Replication of Herpes Simplex Virus 1 and Other DNA and RNA Viruses with Diverse Genomes and Life Cycles.

We utilized a high-throughput cell-based assay to screen several chemical libraries for inhibitors of herpes simplex virus 1 (HSV-1) gene expression. From this screen, four aurora kinase inhibitors were identified that potently reduced gene expression during HSV-1 lytic infection. HSV-1 is known to interact with cellular kinases to regulate gene expression by modulating the phosphorylation and/or activities of viral and cellular proteins.

Pericardial cyst in a one-year-old boy with ventricular septal defect and patent ductus arteriosus.

Background: Pericardial cysts are rare, with the most common etiology being congenital. Ventricular septal defect is the most common congenital heart disease in children. However, the combination of pericardial cyst, ventricular septal defect, and patent ductus arteriosus is extremely rare.

Alteration in Cellular Signaling and Metabolic Reprogramming during Viral Infection.

Cellular activities are finely regulated by numerous signaling pathways to support specific functions of complex life processes. Viruses are obligate intracellular parasites. Each step of viral replication is ultimately governed by the interaction of a virus with its host cells.

Viral growth factor- and STAT3 signaling-dependent elevation of the TCA cycle intermediate levels during vaccinia virus infection.

Metabolism is a crucial frontier of host-virus interaction as viruses rely on their host cells to provide nutrients and energy for propagation. Vaccinia virus (VACV) is the prototype poxvirus. It makes intensive demands for energy and macromolecules in order to build hundreds and thousands of viral particles in a single cell within hours of infection.

A Critically Ill Child with Gangrenous Appendicitis Masquerading as Hollow Viscous Perforation.

Background: Severe complications of acute appendicitis (AA) hitherto well described are less common in clinical practice nowadays. When a septic child is encountered with a short history of abdominal symptoms and disproportionate signs of peritonitis further complicated by radiological findings causing a diagnostic conundrum, management becomes exceedingly demanding. .

The Role of Tape Measure Protein in Nucleocytoplasmic Large DNA Virus Capsid Assembly.

Nucleocytoplasmic large DNA viruses (NCLDVs) are a group of large viruses that infect a wide range of hosts, from animals to protists. These viruses are grouped together in NCLDV based on genomic sequence analyses. They share a set of essential genes for virion morphogenesis and replication.

Asparagine: An Achilles Heel of Virus Replication?

Asparagine biosynthesis and breakdown are tightly regulated in mammalian cells. Recent studies indicate that asparagine supply could be a limiting factor for the replication of some viruses such as vaccinia virus and human cytomegalovirus. In this Viewpoint, we highlight the importance of asparagine metabolism during virus replication and rationalize that asparagine metabolism could be a viable target for broad-spectrum antiviral development.

Identification of Vaccinia Virus Inhibitors and Cellular Functions Necessary for Efficient Viral Replication by Screening Bioactives and FDA-Approved Drugs.

Four decades after the eradication of smallpox, poxviruses continue to threaten the health of humans and other animals. Vaccinia virus (VACV) was used as the vaccine that successfully eradicated smallpox and is a prototypic member of the poxvirus family. Many cellular pathways play critical roles in productive poxvirus replication.

Asparagine Is a Critical Limiting Metabolite for Vaccinia Virus Protein Synthesis during Glutamine Deprivation.

Viruses actively interact with host metabolism because viral replication relies on host cells to provide nutrients and energy. Vaccinia virus (VACV; the prototype poxvirus) prefers glutamine to glucose for efficient replication to the extent that VACV replication is hindered in glutamine-free medium. Remarkably, our data show that VACV replication can be fully rescued from glutamine depletion by asparagine supplementation.

Suppression of Poxvirus Replication by Resveratrol.

Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown.

Seasonal Variation in Essential Oil Compositions and Antioxidant Properties of Acorus calamus L. Accessions.

(Sweet flag) is a known herbal drug commonly used in traditional medicine. Our aim was to perform seasonal and altitudinal phytochemical screening to assess the antioxidant activity of the essential oils in the rhizome and leaves of from three different altitudes. Phytochemical screening was performed using GC/MS analysis and in vitro antioxidant assay was done by different methods.

β-Selinene-Rich Essential Oils from the Parts of Callicarpa macrophylla and Their Antioxidant and Pharmacological Activities.

(Varbenaceae) is a medicinal shrub and is traditionally used in India, China, and South Asia. The plant material was collected from lower Himalayan region of Uttarakhand in India. The essential oils from three different aerial parts were analyzed by GC-MS.

Multidrug resistant Enterobacteriaceae and extended spectrum β-lactamase producing Escherichia coli: a cross-sectional study in National Kidney Center, Nepal.

Background: Emergence of antibacterial resistance and production of Extended spectrum β-lactamases (ESBLs) are responsible for the frequently observed empirical therapy failures. Most countries have experienced rapid dissemination of ESBLs producing Enterobacteriaceae isolates, particularly E. coli and Klebsiella pneumoniae.

neo-Clerodane Diterpenoids from Ajuga macrosperma var. breviflora.

Six new naturally occurring ajugarin-like neo-clerodane diterpenoids, ajugaflorins A-F, along with six known compounds [the parent ajugarin I, ajugalides B and C, ajugamarin F4, ajugamacrin E, and ajugatakasin B] were isolated from A. macrosperma var. breviflora.

Chemical diversity in Mentha spicata: antioxidant and potato sprout inhibition activity of its essential oils.

The essential oils from fresh aerial parts of Mentha spicata L. collected from ten different natural habitats of Uttarakhand, India were analyzed by a combination of GC, GC/MS and NMR spectroscopy. The analysis revealed that monoterpenoids (46.

Chemical diversity in Himalayan Elsholtzia species.

The terpenoid composition of essential oils from the leaves of five Elsholtzia species, viz., E. eriostachya Benth.