Immunology of Infectious Disease News Volume 7.49 | Dec 18 2019

TOP STORY

Repurposing Human Kinase Inhibitors to Create an Antibiotic Active against Drug-Resistant Staphylococcus aureus, Persisters and Biofilms

The authors report screening commercial kinase inhibitors for antibacterial activity and found the anticancer drug sorafenib as major hit that effectively kills methicillin-resistant Staphylococcus aureus strains. [Nat Chem] Abstract | Press Release

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Salmonella Effector SteE Converts the Mammalian Serine/Threonine Kinase GSK3 into a Tyrosine Kinase to Direct Macrophage Polarization

Scientists demonstrated that SteE converted both the amino acid and substrate specificity of the host pleiotropic serine/threonine kinase GSK3. SteE itself was a substrate of GSK3, and phosphorylation of SteE was required for its activity. [Cell Host Microbe] Full Article | Graphical Abstract

Herpesviruses Induce Aggregation and Selective Autophagy of Host Signaling Proteins NEMO and RIPK1 as an Immune-Evasion Mechanism

Researchers showed that the murine cytomegalovirus M45 protein induced the degradation of two cellular signalling proteins, the nuclear factor κ-light-chain-enhancer of activated B cells essential modulator (NEMO) and the receptor-interacting protein kinase 1 (RIPK1), via a different mechanism: it induced their sequestration as insoluble protein aggregates and subsequently facilitated their degradation by autophagy. [Nat Microbiol] Abstract

Maternal Vaccination and Protective Immunity against Zika Virus Vertical Transmission

The authors report maternal vaccination using a live-attenuated Zika virus (ZIKV) vaccine (3ʹUTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3ʹUTR-∆10-LAV did not cause any adverse effects on pregnancy, fetal development, or offspring behavior. [Nat Commun] Full Article

Preferential Presentation of High-Affinity Immune Complexes in Germinal Centers Can Explain How Passive Immunization Improves the Humoral Response

Investigators proposed a mechanism with which passive immunization could alter the humoral response. Antigen-specific B cells evolved and got selected in germinal centers (GCs) on the basis of their ability to acquire antigen from antibody-antigen complexes presented in GCs. [Cell Rep] Full Article | Graphical Abstract

Pre-Existing Neutralizing Antibodies Prevent CD8 T Cell-Mediated Immunopathology following Respiratory Syncytial Virus Infection

To evaluate the ability of respiratory syncytial virus (RSV)-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. [Mucosal Immunol] Full Article

Efficient and Robust NK-Cell Transduction with Baboon Envelope Pseudotyped Lentivector

Transduction with baboon envelope pseudotyped lentiviral vectors encoding for CAR-CD22 resulted in robust CAR-expression on 38.3 ± 23.8% of NK-cell activation and expansion system cells, leading to specific killing of NK-resistant pre-B-ALL-RS4;11 cell line. [Front Immunol] Full Article

Immunity to Influenza Is Dependent on MHC II Polymorphism: Study with 2 HLA Transgenic Strains

Researchers infected autoimmune-susceptible DRB1*0401.AEo and non-susceptible *0402.AEo mice with H1N1 influenza and determined clearance and protective immunity to H3N2 virus. [Sci Rep] Full Article

One-Step Artificial Antigen Presenting Cell-Based Vaccines Induce Potent Effector CD8 T Cell Responses

Investigators tested the idea of whether peptide-major histocompatibility complexes could directly be captured from cell lysates, including cancer cells using affinity beads, and used to initiate T cell responses. [Sci Rep] Full Article

Monocytes Undergo Multi-Step Differentiation in Mice during Oral Infection by Toxoplasma gondii

Scientists evaluated the differentiation process that occurs in Ly6Chi monocytes during oral infection by Toxoplasma gondii. Flow cytometry and single-cell analysis revealed distinct activation status and gene expression profiles in the bone marrow, the spleen and the lamina propria of infected mice. [Commun Biol] Full Article

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B Cell Memory: Building Two Walls of Protection against Pathogens

Researchers describe the two-phase process by which antigen drives the generation of long-lived plasma cells and memory B cells and highlight the challenges for successful vaccine development in each phase. [Nat Rev Immunol] Abstract

You Shall Not Pass: Memory CD8 T Cells in Liver-Stage Malaria

Memory CD8 T cell anatomic localization and expression of transcription factors, homing receptors, and signaling molecules appear to play integral roles in protective immunity to liver-stage malaria. [Trends Parasitol] Abstract

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$1.3 Million to Eliminate Parasitic Worms

Researchers from Australian National University have been awarded $1.3 million by the National Health and Medical Research Council e-Asia Joint Research Program. The team will work toward eliminating parasitic worms and associated liver cancer in communities of the Lower Mekong Basin. [Australian National University] Press Release

First Light Diagnostics Receives Additional Funding from the Biomedical Advanced Research and Development Authority (BARDA)

First Light Diagnostics, Inc. announced the authorization of $4.3 million in additional funding from BARDA in support of First Light’s development of the MultiPath platform, along with diagnostic tests for anthrax and urinary tract infection pathogen identification and culture-free, anti-microbial susceptibility testing. [First Light Diagnostics, Inc.] Press Release

Mycovia Pharmaceuticals Completes Enrollment in Its Third Phase III Clinical Trial for VT-1161 (ultraVIOLET) in Patients with Recurrent Vulvovaginal Candidiasis

Mycovia Pharmaceuticals, Inc. announced it has completed enrollment for its ongoing Phase III ultraVIOLET clinical trial for VT-1161. [Mycovia Pharmaceuticals, Inc.] Press Release

Chinese Institutes Investigate Pathogen Outbreaks in Lab Workers

Two Chinese agriculture research institutions are investigating how more than 100 students and staff became infected with the bacterium Brucella, strains of which are typically found in farm animals but can also trigger potentially fatal complications in people. [Nature News] Editorial

NIH Strategic Plan Details Pathway to Achieving Hepatitis B Cure

The Strategic Plan for Trans-NIH Research to Cure Hepatitis B focuses on three key research areas. The first priority calls for a better understanding of hepatitis B biology, including the viral and host factors that lead to disease, immunity, reactivation and transmission, as well as the impact of co-infections with other hepatitis viruses and HIV. An improved understanding of these factors and the HBV lifecycle is essential to developing a cure. [National Institutes of Health] Editorial

NEW Translational Research in Viral Hepatitis: Addressing the Gaps for Cure
January 23-25, 2020
Athens, Greece

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NEW Postdoctoral Fellowship – Infectious Disease (Brigham and Women’s Hospital)

NEW Postdoctoral Fellows – Molecular Microbiology and Antibiotic Resistance (University of Gothenburg)

NEW PhD & MD/PhD Positions – Immunology & Infectious Diseases (Research Training Group 1949)

Postdoctoral Research Fellow – HIV (Fred Hutchinson Cancer Research Center)

Research Fellow – Immune Response to Tuberculosis (University College London)

Senior Lecturer – Infectious Disease and Microbiomes (University of Liverpool)

Postdoctoral Fellow – Cerebral Malaria (European Molecular Biology Laboratory)

Postdoctoral Positions – HIV (University of New South Wales)

Faculty Position – Infectious Disease Research (Tsinghua University School of Medicine)

Postdoctoral Associates – Virology and Vaccine Development (University of Minnesota)

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