Immunology of Infectious Disease News Volume 3.09 | Mar 11 2015

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

HIV

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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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

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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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