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Related Articles from SNS
Differential Sensitivity of HSV-1 and PRV to IFN-{lambda} Reveals a Neuron-Specific Antiviral Role for RSAD2
Alpha herpesviruses (-HV) initially infect mucosal epithelial cells and subsequently establish lifelong latency in the peripheral nervous system (PNS). Herpes simplex virus-1 (HSV-1), a human pathogen persisting in the majority of the adult population, shares neuroinvasive properties with Pseudorabies virus (PRV), a swine -HV, commonly used as a model -HV. Utilizing primary peripheral neuronal cultures, we previously showed that IFN-{lambda} pre-treatment significantly reduced PRV yield.
Tracing the Evolutionary Origin of Interferon to Basal Chordates and Unveiling Its Antiviral Functionality in Jawless Vertebrates
Interferons (IFNs) are essential mediators of antiviral defense in vertebrates, having gradually replaced the RNA interference (RNAi) antiviral mechanism that predominates in invertebrates and plants. To date, IFNs have been identified exclusively in jawed vertebrates, leaving the origin of IFN-based antiviral mechanisms largely mysterious. In this study, by conducting a genome-wide screening of IFN homologs accross various species, we successfully identified seveal IFN homologs from agnatha...
A novel tumor-targeted interferon-α/-β receptor 1 antagonist increases replication of oncolytic vesicular stomatitis virus in a mouse mesothelioma model
Type I Interferons (IFN-I) are cytokines with pleiotropic activities involved in antiviral and antitumor immune responses. They can reduce oncolytic virus replication in tumor cells by inducing expression of interferon stimulated genes (ISG) with antiviral functions. To specifically neutralize the IFN-/-{beta} receptor (IFNAR) on specific cell types, we created novel IFNAR1-targeted antagonists constituted of a high-affinity nanobody targeting a specific cell surface marker conjugated to a...
Transcriptionally Active HIV Reservoirs Enriched for Interferon-Inducible APOBEC3-Related Mutational Signatures Associate with Reduced Neuroaxonal Integrity
Despite sustained viral suppression with effective antiretroviral therapy (ART), neuroaxonal integrity persist in a subset of people with HIV-1 (PWH). We investigated whether interferon (IFN)-inducible APOBEC3-associated mutational signatures, reflected by premature stop codons (PSCs), and reservoir-associated drug resistance mutations (RS-DRMs) within transcriptionally active HIV-1 reservoirs influence neuroaxonal integrity in fully virally suppressed individuals. Peripheral CD4 T cells...
Modulation of Ferroptosis During Early Mycobacterium tuberculosis Infection Contributes to Beijing Lineage Strain SA161 Virulence
Although spread of internalized Mtb from the initial infected alveolar macrophages (AMs) is a crucial determinant of infection outcomes, the role of cell death in facilitating this spread, and how it is regulated by Mtb remains poorly understood. Ferroptosis, a lipid peroxidation-mediated form of necrotic cell death, contributes to pathology during later stages of infection. However, the role of ferroptosis in early AM cell death remains inadequately defined, and its induction during...
EGFR INHIBITION PROMOTES ENTEROENDOCRINE CELL DIFFERENTIATION CONTRIBUTING TO TREATMENT-ASSOCIATED DIARRHEA
Enteroendocrine cells (EECs) are specialized sensors of the gastrointestinal (GI) epithelium that regulate gut function and systemic metabolism through hormone secretion. The molecular pathways directing intestinal stem cell (ISC) differentiation into EECs are incompletely understood due, in part, to their rarity. We sought to identify novel regulators of human EEC differentiation using a high-throughput screen of FDA-approved drugs and human duodenal organoids.
Characterization of expression elements for an AAV delivered antibody in nonhuman primates when co-delivered with PD-L1
Successful AAV-expressed antibody therapy for HIV-1 requires broadly neutralizing antibody (bNAbs) concentrations and reduced immune responses to sustain viral suppression without ART. We have previously demonstrated that co-delivery of AAV-expressed PD-L1 reduces immune responses against HIV-1 bNAbs in rhesus macaques. Here we systematically evaluated six AAV9 transgene cassettes encoding 10-1074 with different promoter/intron combinations (CMV, CMV/R, CBA, CASI, CB7, EF1a) across in vitro...
Clinical isolates of Mycobacterium avium complex reveal an M. intracellulare-associated IL-17/neutrophilic pulmonary immune program in a murine disease model
Mycobacterium avium complex (MAC) is the leading cause of nontuberculous mycobacterial pulmonary disease (NTM-PD) and mainly comprises M. avium (MAV) and M. intracellulare (MI). Host-pathogen interactions may contribute to the heterogeneous clinical course of MAC pulmonary disease (MAC-PD); however, species- or isolate-associated differences in virulence and host immune responses induced by MAC strains remain poorly understood. Here, we established a panel of MAC clinical isolates exhibiting...