Volume 3.09 | Mar 11

Immunology of Infectious Disease News 3.09 March 11, 2015
Immunology of Infectious Disease News
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Human Ebola Virus Infection Results in Substantial Immune Activation
Researchers have obtained a first look at the immune responses in four Ebola virus disease survivors who received care at Emory University Hospital in 2014, by closely examining their T cells and B cells during the acute phase of the disease. [Press release from Emory University discussing online prepublication in Proceedings of the National Academy of Sciences] Press Release | Abstract | Full Article
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PUBLICATIONS (Ranked by impact factor of the journal)
Sox2 Functions as a Sequence-Specific DNA Sensor in Neutrophils to Initiate Innate Immunity against Microbial Infection
Investigators found constitutive expression of the transcription factor Sox2 in the cytoplasm of mouse and human neutrophils. Neutrophil-specific Sox2 deficiency exacerbated bacterial infection. [Nat Immunol] Abstract

CXCR3 Chemokine Receptor Enables Local CD8+ T Cell Migration for the Destruction of Virus-Infected Cells
Researchers examined the environmental signals that CD8+ T cells use to localize and eliminate virus-infected skin cells. Despite normal T cell numbers in the skin, Cxcr3−/− mice exhibited dramatically impaired CD8+-T-cell-dependent virus clearance. [Immunity] Abstract

Virus-Specific T Lymphocytes Home to the Skin during Natural Dengue Infection
Researchers showed that natural infection induced dengue-specific CD8+ T lymphocytes that were highly activated and proliferating, exhibited antiviral effector functions, and expressed CXCR3, CCR5, and the skin-homing marker cutaneous lymphocyte-associated antigen. [Sci Transl Med] Abstract

CXCR3 Blockade Protects against Listeria monocytogenes Infection-Induced Fetal Wastage
Scientists demonstrated that fetal wastage triggered by prenatal L. monocytogenes infection is driven by placental recruitment of CXCL9-producing inflammatory neutrophils and macrophages that promote infiltration of fetal-specific T cells into the decidua. [J Clin Invest] Full Article | Press Release

Herpes Simplex Type 2 Virus Deleted in Glycoprotein D Protects against Vaginal, Skin and Neural Disease
To test the hypothesis that deletion of glycoprotein D (gD-2) unmasks protective antigens, scientists evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD. [eLife] Full Article | Editorial | Press Release

T-Cell Reprogramming through Targeted CD4-Coreceptor and T-Cell Receptor Expression on Maturing Thymocytes by Latent Circoviridae Family Member Porcine Circovirus Type 2 Cell Infections in the Thymus
To elucidate virus pathogenicity, investigators developed a new pig infection model by in vivo transfection of recombinant porcine circovirus type 2 (PCV2) and the immunosuppressant cofactor cyclosporine A. Using flow cytometry, immunofluorescence and fluorescence in situ hybridization, they found evidence that PCV2 dictates positive and negative selection of maturing T cells in the thymus. [Emerg Microbes Infect] Full Article

Clinical Testing of a Dendritic Cell Targeted Therapeutic Vaccine in Patients with Chronic Hepatitis C Virus Infection
Due to the central role that dendritic cells (DC) play in the activation of T-cell responses, scientists aimed to carry out a therapeutic vaccination clinical trial in hepatitis C virus patients using DC. [Mol Ther Methods Clin Dev] Full Article


Use of the CRISPR/​Cas9 System as an Intracellular Defense against HIV-1 Infection in Human Cells
Investigators adapted the CRISPR/​Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, their results demonstrate that the CRISPR/​Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. [Nat Commun] Abstract | Press Release

NFκB Activation by Modified Vaccinia Virus as a Novel Strategy to Enhance Neutrophil Migration and HIV-Specific T-Cell Responses
Scientists generated an attenuated vaccinia virus strain that expresses HIV-1 clade C antigens but lacks three specific viral genes. They found that these genes act together to inhibit the NFκB signaling pathway. Triple ablation in modified virus restored NFκB function in macrophages. [Proc Natl Acad Sci USA] Abstract

Cell-Specific RNA Aptamer against Human CCR5 Specifically Targets HIV-1 Susceptible Cells and Inhibits HIV-1 Infectivity
Scientists combined the live-cell-based SELEX with high-throughput sequencing technology to generate C-C chemokine receptor type 5 (CCR5) RNA aptamers capable of specifically targeting HIV-1 susceptible cells and inhibiting HIV-1 infectivity via block of the CCR5 required for HIV-1 to enter cells. The best candidate, G-3, specifically neutralized R5 virus infection in primary peripheral blood mononuclear cells, and in vivo generated human CD4+ T cells. [Chem Biol] Abstract | Graphical Abstract

The Influence of Pediatric HIV Infection on Circulating B-Cell Subsets and CXCR5+ T-Helper Cells
Investigators assessed B and T-cell phenotype in a cohort of children from a single center in the UK with perinatally acquired HIV compared to healthy controls. The majority of HIV infected children were on fully suppressive combination antiretroviral therapy. [Clin Exp Immunol] Abstract

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Now You See Me, Now You Don’t: The Interaction of Salmonella with Innate Immune Receptors
The authors compare and contrast the interactions of Salmonella Typhi and non-typhoidal Salmonella (NTS) serovars with host innate immune receptors and discuss why the disease manifestations associated with S. Typhi infection differ considerably from those associated with the closely related NTS serovars. [Nat Rev Microbiol] Abstract

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.
Sangamo BioSciences Presents New Clinical Data from Trial of ZFP Therapeutic® Designed to Provide Functional Control of HIV
Sangamo BioSciences, Inc. announced the presentation of new clinical data from its Phase I/II clinical trial. The study was designed to evaluate SB-728-T, a ZFP Therapeutic® generated by ZFN-mediated genome editing of T-cells to knockout the CCR5 gene, which encodes a critical co-receptor for HIV infection. [Press release from Sangamo BioSciences, Inc. discussing research presented at the Conference on Retroviruses and Opportunistic Infections (CROI 2015), Seattle] Press Release

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New Trial of TKM-Ebola Treatment to Start in Sierra Leone
A clinical trial of a potential Ebola therapy called TKM-Ebola-Guinea will start today in Sierra Leone. The Phase II study is the second drug trial to be funded through the Wellcome Trust’s £3.2 million Ebola therapeutics platform. [Wellcome Trust] Press Release

NIH-Led Study to Assess Community-Based Hepatitis C Treatment in Washington, D.C.
Officials from the National Institutes of Health and the city of Washington, D.C., launched a clinical trial to examine whether primary care physicians and other health care providers can use a new antiviral therapy as effectively as specialist physicians to treat people with hepatitis C virus infection. [National Institutes of Health] Press Release

FDA Approves New Antifungal Drug Cresemba
The U.S. Food and Drug Administration (FDA) approved Cresemba (isavuconazonium sulfate), a new antifungal drug product used to treat adults with invasive aspergillosis and invasive mucormycosis, rare but serious infections. [U.S. Food and Drug Administration] Press Release
National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)
NEW International Congress of Mucosal Immunology (ICMI) 2015
July 14-18, 2015
Berlin, Germany

Visit our events page to see a complete list of events in the immunology of infectious disease community.
NEW Manufacturing Manager – Cell Therapy (Opexa Therapeutics)

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

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

PhD Studentship – Innate Lymphoid Cells (University of Birmingham)

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)

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