Host-Microbe Biology
Research Article | Host-Microbe BiologyGamma Interferon Alters Junctional Integrity via Rho Kinase, Resulting in Blood-Brain Barrier Leakage in Experimental Viral EncephalitisIn an experimental viral encephalitis mouse model in which mice are infected with reovirus, we show that IFN-γ induces blood-brain barrier leakage. We show that IFN-γ promotes Rho kinase activity, resulting in actin cytoskeletal contractions in the brain endothelium that lead to vascular junctional disorganization and cell-cell separations. These studies now provide insight into a previously unknown mechanism for how blood-brain barrier...
Research Article | Host-Microbe BiologyEfficient Inhibition of Human Papillomavirus Infection by L2 Minor Capsid-Derived LipopeptideHPV is a human oncogenic virus that causes a major public health problem worldwide, which is responsible for approximately 5% of total human cancers and almost all cases of cervical cancers. HPV capsid consists of two structure proteins, the major capsid L1 protein and the minor capsid L2 protein. While L2 plays critical roles during the viral life cycle, the molecular mechanism in viral entry remains elusive. Here, we performed fine...
Research Article | Host-Microbe BiologyDisruption of Glycolysis by Nutritional Immunity Activates a Two-Component System That Coordinates a Metabolic and Antihost Response by Staphylococcus aureusTwo-component regulatory systems enable bacteria to adapt to changes in their environment during infection by altering gene expression and coordinating antihost responses. Despite the critical role of two-component systems in bacterial survival and pathogenesis, the activating signals for most of these regulators remain unidentified. This is exemplified by ArlRS, a ...
Research Article | Host-Microbe BiologyA Chaperone for the Stator Units of a Bacterial FlagellumThe bacterial flagellum is a reversible rotating motor powered by ion transport through stator units, which also exert torque on the rotor component to turn the flagellum for motility. Species-specific adaptations to flagellar motors impact stator function to meet the demands of each species to sufficiently power flagellar rotation. We identified another evolutionary adaptation by discovering that FlgX of...
Research Article | Host-Microbe BiologyRole of Toxoplasma gondii Chloroquine Resistance Transporter in Bradyzoite Viability and Digestive Vacuole MaintenanceIndividuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk of experiencing reactivated disease that can result in progressive loss of vision. No effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of the biology underlying chronic infection and a lack of well-validated potential targets. We show...
Research Article | Host-Microbe BiologyAnopheles Salivary Gland Architecture Shapes Plasmodium Sporozoite Availability for TransmissionMalaria continues to have a devastating impact on human health. With growing resistance to insecticides and antimalarial drugs, as well as climate change predictions indicating expansion of vector territories, the impact of malaria is likely to increase. Additional insights regarding pathogen migration through vector mosquitoes are needed to develop novel methods to prevent transmission to new hosts. Pathogens, including the microbes...
Research Article | Host-Microbe BiologyHepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122Chronic hepatitis C virus (HCV) infection is a major global public health problem. Infection often leads to severe liver injury that may progress to cirrhosis, hepatocellular carcinoma, and death. HCV coopts cellular machineries for propagation and triggers pathological processes in the liver. We previously identified a pivotal role of IKK-α in regulating cellular lipid metabolism and HCV assembly. In this study, we characterized NIK as...
Research Article | Host-Microbe BiologyPseudomonas aeruginosa Increases the Sensitivity of Biofilm-Grown Staphylococcus aureus to Membrane-Targeting Antiseptics and AntibioticsThe thick mucus in the airways of cystic fibrosis (CF) patients predisposes them to frequent, polymicrobial respiratory infections. Pseudomonas aeruginosa and Staphylococcus aureus are frequently coisolated from the airways of individuals with CF, as well as from diabetic foot ulcers and other...
Research Article | Host-Microbe BiologyEndogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA ExpressionEndogenous retroviruses are transposable genetic elements comprising 8% to 10% of the human and mouse genomes. Although most ERVs have been inactivated due to deleterious mutations, some are still transcribed. However, the biological functions of transcribed ERVs are largely unknown. Here, we identified a full-length ERV-derived lncRNA, designated lnc-EPAV, as a positive regulator of host innate immune responses. We found that silencing...
Research Article | Host-Microbe BiologyDissecting the Gene Expression, Localization, Membrane Topology, and Function of the Plasmodium falciparum STEVOR Protein FamilyMalaria claims about half a million lives each year. Plasmodium falciparum, the causative agent of the most severe form of the disease, uses proteins that are translocated to the surface of infected erythrocytes for immune evasion. To circumvent the detection of these gene products by the immune system, the parasite evolved a complex strategy that includes gene...