Immunology of Infectious Disease News Volume 5.38 | Sep 27 2017

TOP STORY

Germline Bias Dictates Cross-Serotype Reactivity in a Common Dengue-Virus-Specific CD8⁺ T Cell Response

Scientists found that clonotypes expressing the T cell antigen receptor β-chain variable region 11 were ‘preferentially’ activated and mobilized within immunodominant human-leukocyte-antigen–A*11:01-restricted CD8⁺ T cell populations specific for variants of the nonstructural protein epitope NS3₁₃₃ that characterize the serotypes dengue virus (DENV)1, DENV3 and DENV4. [Nat Immunol] Abstract

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Inhibition of EBV-Mediated Membrane Fusion by Anti-gHgL Antibodies

Researchers studied the structures and mechanisms of two anti-gHgL antibodies, CL40 and CL59, that block membrane fusion with both B cells and epithelial cells. CL40 binding to gHgL/gp42 complexes was not blocked by gp42 and did not interfere with gp42 binding to HLA class II, indicating that its ability to block membrane fusion with B cells represents a defect in gB activation. [Proc Natl Acad Sci USA] Abstract

Mycobacterium tuberculosis Controls Phagosomal Acidification by Targeting CISH-Mediated Signaling

The authors present evidence that M. tuberculosis resorts to a strategy to control phagosomal acidification, interfering with host suppressor of cytokine signaling protein functions. They showed that infection of macrophages with M. tuberculosis leads to granulocyte-macrophage colony-stimulating factor secretion, inducing STAT5-mediated expression of cytokine-inducible SH2-containing protein (CISH), which selectively targets the V-ATPase catalytic subunit A for ubiquitination and degradation by the proteasome. [Cell Rep] Full Article | Graphical Abstract

Ebola Virus Binding to Tim-1 on T Lymphocytes Induces a Cytokine Storm

A series of in vitro assays based on the T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) expression profile on T cells demonstrated that despite the apparent absence of detectable viral replication in T lymphocytes, Ebola virus directly binds to isolated T lymphocytes in a phosphatidylserine–Tim-1-dependent manner. [MBio] Full Article | Press Release

Anti-Mycobacterial Activity Correlates with Altered DNA Methylation Pattern in Immune Cells from BCG-Vaccinated Subjects

Scientists investigated whether epigenetic mechanisms are involved in the response of immune cells to the Bacille Calmette-Guerin (BCG) vaccine. They isolated peripheral blood mononuclear cells from BCG-vaccinated subjects and performed global DNA methylation analysis in combination with functional assays representative of innate immunity against Mycobacterium tuberculosis infection. [Sci Rep] Full Article

Skin Infections Are Eliminated by Cooperation of the Fibrinolytic and Innate Immune Systems

Investigators showed that early activation of nuclear factor of activated T cells balances the two major phases of the innate response to Candida albicans skin infections: the protective containment (abscess) and the elimination (expulsion) phases. [Sci Immunol] Full Article

HIV

p21 Restricts HIV-1 in Monocyte-Derived Dendritic Cells through the Reduction of dNTP Biosynthesis and Regulation of SAMHD1 Antiviral Activity

Researchers showed that inhibition of HIV-1 replication in monocyte-derived dendritic cells (DCs) is associated to an increased expression of p21cip1/waf, a cell cycle regulator that is involved in the differentiation and maturation of DCs. [J Virol] Abstract

Insights into the Impact of CD8⁺ Immune Modulation on HIV Evolutionary Dynamics in Distinct Anatomical Compartments Using SIV-Infected Macaque Models of AIDS Progression

Using several different phylogenetic methods, scientists analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from simian immunodeficiency virus (SIV)mac251-infected macaques, with or without CD8⁺ lymphocyte depletion. [J Virol] Abstract

Elevated Humoral Response to Cytomegalovirus in HIV-Infected Individuals with Poor CD4⁺ T-Cell Immune Recovery

Some HIV-infected combination antiretroviral therapy (c-ART)-suppressed individuals show incomplete CD4⁺ T-cell recovery, abnormal T-cell activation and higher mortality. One potential source of immune activation could be coinfection with cytomegalovirus (CMV). IgG and IgM levels, immune activation, inflammation and T-cell death in c-ART-suppressed individuals with CD4⁺ T-cell counts >350 cells/μL or <350 cells/μL were analyzed to evaluate the effect of CMV humoral response on immune recovery. [PLoS One] Full Article

Development and Optimization of a Sensitive Pseudovirus-Based Assay for HIV-1 Neutralizing Antibodies Detection Using A3R5 Cells

Scientists developed an easy-to-use HIV-1 pseudovirus neutralization assay based on a human CD4⁺ lymphoblastoid cell line A3R5 by employing a high efficient pseudovirus production system. Optimal conditions for cell counts, infection time, virus dose and concentration of DEAE-dextran were tested and identified. For T-cell line-adapted tier 1 virus strains, significantly higher inhibitory efficiency was observed for both monoclonal neutralizing antibody and plasma samples in A3R5 than those in TZM-bl assay. [Hum Vaccin Immunother] Abstract

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Host-Directed Therapies for Bacterial and Viral Infections

The authors describe current progress in the development of host-directed therapy for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic. [Nat Rev Drug Discov] Abstract

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Nearly $6.3 Million Grant to Expand Promising Ebola Vaccine Research Awarded to UH Researcher

University of Hawaii (UH) vaccine researcher Axel Lehrer, has received a $6.35 million grant to test whether the Ebola vaccine formula he has developed will protect against two additional viruses in the same family. [University of Hawaii] Press Release | Video

Soligenix Announces $700,000 Subaward Supporting Development Collaboration on Thermostabilization of an Ebola Vaccine Candidate

Soligenix, Inc. announced that Soligenix will be participating in a Research Project grant awarded to the University of Hawai’i at Manoa for the development of a thermostabilized Ebola vaccine, with Soligenix awarded funding of approximately $700,000 over five years. [Soligenix, Inc.] Press Release

BioCryst’s RAPIVAB^® (Peramivir Injection) Receives FDA Approval for a Pediatric Indication

BioCryst Pharmaceuticals, Inc. announced that the FDA has approved a supplemental New Drug Application for RAPIVAB, an intravenous neuraminidase inhibitor, extending its availability for the treatment of acute uncomplicated influenza to pediatric patients two years and older who have been symptomatic for no more than two days. [BioCryst Pharmaceuticals, Inc.] Press Release

European Commission Approves Symtuza^® for the Treatment of HIV-1 in Adults and Adolescents in Europe

Janssen-Cilag International NV (Janssen) announced that the European Commission has approved the use of Symtuza^®, a once-daily darunavir-based single-tablet regimen, for the treatment of HIV-1 infection in adults and adolescents aged 12 years and older with body weight of at least 40 kg. [Janssen-Cilag International NV (Janssen) (Business Wire, Inc.)] Press Release

Senate Panel Blocks NIH from Revising Translational Research Awards

A congressional spending panel has backed scientists running a $516 million network of bench-to-bedside research centers in their fight with the National Institutes of Health (NIH) in Bethesda, Maryland, over how it manages the network. It’s the latest step in a long-running tug-of-war over the direction of the Clinical and Translational Science Awards program. [ScienceInsider] Editorial

Canada Names New Chief Science Adviser

Mona Nemer, a cardiology researcher and vice-president of research at the University of Ottawa, has been named Canada’s new Chief Science Adviser by Prime Minister Justin Trudeau. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Biology of Host-Parasite Interactions
June 10-15, 2018
Newport, Rhode Island, United States

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NEW Assistant Professor – Infectious Disease (J. Craig Venter Institute)

NEW Professor – Clinical Infectious Diseases (Westfälische Wilhelms-Universität Münster)

Scientist – Immunology (STEMCELL Technologies Inc.)

Research Technologist – Immunotherapy (STEMCELL Technologies Inc.)

Full Professorship – Infection, Inflammation and Cancer (German Cancer Research Center)

Postdoctoral Fellow/Staff Scientist – Tuberculosis Research (Washington University School of Medicine)

Postdoctoral Fellow – Immunology (Johns Hopkins University)

Postdoctoral Position – Autophagy (University of New Mexico)

PhD Positions – Cancer, Infection and Immunity, and Tissue Regeneration Research (Virginia Commonwealth University)

Professorship – Infection Biology (Hannover Medical School)

Postdoctoral Scientist – Immunology/Microbial Pathogenesis (Nationwide Children’s Hospital)

Assistant or Associate Professor – Virology (University of Iowa)

Faculty Positions – Host-Pathogen Interactions (University of Chicago at Illinois)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte. Ltd.)

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