Immunology of Infectious Disease News Volume 3.08 | Mar 4 2015

A Bacterial Cyclic Dinucleotide Activates the Cytosolic Surveillance Pathway and Mediates Innate Resistance to Tuberculosis
Investigators found that a di-adenylate cyclase 4-overexpressing Mycobacterium tuberculosis strain that secretes excess cyclic-di-adenosine monophosphate activated the interferon regulatory factor pathway with enhanced levels of IFN-β, elicited increased macrophage autophagy, and exhibited substantial virulence attenuation in mice. [Nat Med] Abstract | Press Release

Human Monocytes Undergo Functional Re-Programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α
Investigators performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Their results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. [Immunity]
Abstract | Graphical Abstract

Cutaneous Na⁺ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense
Scientists used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na⁺ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase-dependent nuclear factor of activated T cells 5 activation. [Cell Metab]
Full Article | Graphical Abstract | Press Release

​IL-10 Inhibits ​Neuraminidase-Activated TGF-β and Facilitates Th1 Phenotype during Early Phase of Infection
In an antigen-specific mouse experimental system, influenza ​hemagglutinin-specific ​CD4⁺ T cells responded to infection with the induction of ​T-bet, and produced both ​IFN-γ and ​IL-10. In the early phase of infection, an abundance of viral ​neuraminidase caused TGF-β activation of ​hemagglutinin-specific ​CD4⁺ T cells. [Nat Commun] Abstract

Generation of Cellular Immune Memory and B-Cell Immunity Is Impaired by Natural Killer Cells
Investigators showed that mouse natural killer cells inhibit generation of long-lived virus-specific memory T- and B cells as well as virus-specific antibody production after acute infection. [Nat Commun] Abstract

Viral Entry Route Determines How Human Plasmacytoid Dendritic Cells Produce Type I Interferons
Scientists showed that replication of the yellow fever live vaccine YF-17D in human plasmacytoid dendritic cells (pDCs) and pDC-like cell lines stimulated type I interferon production through RIG-I (retinoic acid-inducible gene I), a member of the RIG-I-like receptor family of cytosolic pattern recognition receptors. [Sci Signal] Abstract

HIV

An Evolutionary Role for HIV Latency in Enhancing Viral Transmission
Mathematical modeling indicates that HIV’s Tat positive-feedback circuitry enables this persistence and strongly controls latency. To overcome the inherent crosstalk between viral circuitry and cellular activation and to directly test this hypothesis, investigators synthetically decoupled viral dependence on cellular environment from viral transcription. [Cell] Abstract | Graphical Abstract | Press Release

Large Number of Rebounding/Founder HIV Variants Emerge from Multifocal Infection in Lymphatic Tissues after Treatment Interruption
Scientists examined lymph node and gut-associated lymphoid tissue (LT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive cells were detected by in situ hybridization in LTs obtained before interruption in several patients. [Proc Natl Acad Sci USA] Abstract | Full Article

Early Antiretroviral Therapy with Raltegravir Generates Sustained Reductions in HIV Reservoirs but Not Lower T-Cell Activation Levels
Investigators conducted an open-label, nonrandomized study, monitoring for three years: plasma viral load, T-cell phenotypes, and peripheral CD4⁺ T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. [AIDS] Abstract

Analysis of Protein Kinase C Theta Inhibitors for the Control of HIV-1 Replication in Human CD4⁺ T Cells Reveals an Effect on Retrotranscription in Addition to Viral Transcription
Scientists found that protein kinase C theta (PKCθ) activity increased viral replication, but also that HIV-1 induced higher activation of PKCθ in infected CD4⁺ T cells, creating a feedback loop. [Biochem Pharmacol] Abstract

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Infectious Mononucleosis
Infectious mononucleosis is a clinical entity characterized by pharyngitis, cervical lymph node enlargement, fatigue and fever, which results most often from a primary Epstein-Barr virus (EBV) infection. Future research goals are development of an EBV vaccine, understanding the risk factors for severity of the acute illness and likelihood of developing cancer or autoimmune diseases, and discovering anti-EBV drugs to treat infectious mononucleosis and other EBV-spurred diseases. [Clin Transl Immunol] Full Article

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$2.5 Million NIH Grant to Fund Mount Sinai Research into Reducing Heroin Injection and HIV Infection
The National Institute on Drug Abuse has awarded Don C. Des Jarlais, PhD, a 2015 Avant-Garde Award. Dr. Des Jarlais will receive a grant of $500,000 per year for five years to lead a HIV prevention study in two cities contending with growing heroin use: New York City and Tallinn, Estonia. [Icahn School of Medicine at Mount Sinai] Press Release

CIRM-Funded Clinical Trial Aimed at Blocking HIV/AIDS in People Gets the Go Ahead
An innovative therapy using a patient’s own stem cells, modified to resist infection with the AIDS virus, has been given approval by the Food and Drug Administration to begin a clinical trial in people. CIRM, California’s stem cell agency, is funding that trial. [California Institute for Regenerative Medicine] Press Release

VG Life Sciences Granted Key Composition Of Matter Patent
U.S. Patent No. 8957031 covers the targeted peptide technology underlying VG Life Sciences’ VG1177, a synthetic peptide which has the ability to displace CLIP (Class II-associated invariant chain peptide) that plays a key role in chronic inflammation and autoimmune diseases, including HIV/AIDS, hypertension, preeclampsia and traumatic brain injury. [VG Life Sciences (PR Newswire Association LLC)] Press Release

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NIH Moving Ahead with Review of Risky Virology Studies
Last fall, in a startling move, the U.S. government announced that a handful of U.S.-funded studies on risky pathogens were so dangerous that researchers should halt the work until experts could review them. After weeks of quiet, that review now appears to be moving forward. [ScienceInsider] Editorial

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Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

PhD Studentship – Host Genetic Regulation of Viral Infection of Importance for Development of Multiple Sclerosis (Karolinska Institutet)

Postdoctoral Fellow – Infection and Immunity (Wuhan Institute of Virology)

Postdoctoral Fellow – Cytokine Signaling (Inserm)

PhD Studentship – Characterization of the Immediate Early Response of Human Dendritic Cells to Candida albicans (International Leibniz Research School)

Director – Vector Production (Sangamo BioSciences, Inc.)

Senior Process Development Engineer (Sangamo BioSciences, Inc.)

Postdoctoral Fellow – Innate and Adaptive Immune Mechanisms of Viral Persistence and Cancer (Princess Margaret Cancer Centre)

Postdoctoral Position – Innate Immune Signaling in Pathogen Infection (Sanford-Burnham Medical Research Institute)

Postdoctoral Fellow – Mechanisms of HIV-1 Immune Control and Dendritic Cell Immunopathology in HIV-1 Infection (Massachusetts General Hospital)

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