Immunology of Infectious Disease News Volume 3.15 | Apr 22 2015

Alveolar Macrophage-Derived Type I Interferons Orchestrate Innate Immunity to RSV through Recruitment of Antiviral Monocytes
Scientists showed that alveolar macrophages (AMs) are the major source of type I interferons upon respiratory syncytial virus (RSV) infection in mice. AMs detect RSV via mitochondrial antiviral signaling protein (MAVS)-coupled retinoic acid-inducible gene 1-like receptors, and loss of MAVS greatly compromises innate immune restriction of RSV. [J Exp Med] Abstract

PD-1 Co-Inhibitory and OX40 Co-Stimulatory Crosstalk Regulates Helper T Cell Differentiation and Anti-Plasmodium Humoral Immunity
Researchers showed that malaria patients and Plasmodium-infected rodents exhibit atypical expression of the co-stimulatory receptor OX40 on CD4 T cells and that therapeutic enhancement of OX40 signaling enhances helper CD4 T cell activity, humoral immunity, and parasite clearance in rodents. [Cell Host Microbe]
Abstract | Graphical Abstract

Eliminating Hepatitis B by Antagonizing Cellular Inhibitors of Apoptosis
Scientists showed that the clinical-stage drug birinapant, which antagonizes host cell inhibitor of apoptosis proteins, preferentially promotes the killing of hepatitis B virus (HBV)-infected hepatocytes in a mouse model of HBV. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Adaptive Immune-Mediated Host Resistance to Toxoplasma gondii Is Governed by the NF-κB Regulator Bcl-3 in Dendritic Cells
Researchers showed that Bcl-3 expression in dendritic cells is required to generate a protective Th1-type immune response and confer resistance to T. gondii. Surprisingly, mice lacking Bcl-3 in dendritic cells were as susceptible as mice globally deficient for Bcl-3. [Eur J Immunol] Abstract

HIV

Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific CD8 T Cell Population in Elite Controllers
Investigators assessed co-expression of PD-1, Lag-3, CD160 and 2B4 as a measure of T cell exhaustion in a cohort of HIV elite controllers compared to chronic progressors. [J Infect Dis] Abstract

Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity
Researchers describe a novel bispecific chimeric antigen receptor in which a CD4 segment is linked to a single chain variable fragment of the 17b human monoclonal antibody recognizing a highly conserved CD4-induced epitope on gp120 involved in coreceptor binding. [J Virol] Abstract

Stable Phenotypic Changes of the Host T Cells Are Essential to the Long-Term Stability of Latent HIV-1 Infection
Investigators demonstrate that host-cells of latent HIV-1 infection events were functionally altered in ways that are consistent with the idea of an anergic, unresponsive T cell phenotype. [J Virol] Abstract

Histone Deacetylase Inhibitor Romidepsin Inhibits De Novo HIV-1 Infections
A potential concern is that reversing HIV latency with an histone deacetylase inhibitor may reactivate the virus in anatomical compartments with sub-optimal combination antiretroviral therapy concentrations leading to de novo infection of susceptible cells in these sites. Scientists tested physiologically relevant romidepsin concentrations known to reactivate latent HIV in order to definitively address this concern. [Antimicrob Agents Chemother] Abstract

Attrition of TCR Vα7.2⁺ CD161⁺⁺ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression
Researchers conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161⁺⁺CD8⁺ T cells among anti-retroviral therapy (ART)/anti-tuberculosis (TB) therapy treatment-naïve human immunodeficiency virus type (HIV)/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls by flow cytometry. [PLoS One] Full Article

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The Innate Immune Roles of Host Factors TRIM5α and Cyclophilin A on HIV-1 Replication
The authors aimed to comprehensively discuss the sensing and immune activation procedures of TRIM5α innate signaling pathway through Cyclophilin A. They then present the production of TRIMCyp chimeric gene and the different fusion patterns in primates. [Med Microbiol Immunol] Abstract

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Mymetics-Led Consortium Awarded €8.4 Million for Development of Thermo Stable and Cold-Chain Independent Vaccines
Mymetics Corporation announced that its subsidiary Mymetics BV in the Netherlands is leading a consortium that has been selected to receive project grants with a total value of €8.4 million. The grants will fund the evaluation, development and manufacturing scale-up of thermo stable and cold-chain independent nano-pharmaceutical virosome-based vaccine candidates. [Mymetics Corporation (B3C Newswire)] Press Release

Inovio Pharmaceuticals and Roche Initiate Clinical Trial for Inovio’s DNA Immunotherapy to Treat Chronic Hepatitis B Infection
Inovio Pharmaceuticals, Inc. announced that it has initiated a Phase I trial to evaluate Inovio’s DNA immunotherapy in patients who are chronically infected with hepatitis B. [Inovio Pharmaceuticals, Inc.] Press Release

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NEW Postdoctoral Fellow – HIV Resistant Macrophages (Leidos Biomedical Research, Inc.)

NEW Postdoctoral Position – Immunology/Virology (Inserm)

NEW Early Stage Researcher – Identification and Characterization of Hepatitis B Virus Inhibitors (AiCuris GmbH)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Position – Immuno-Metabolism (East Carolina University)

Postdoctoral Position – Immune Responses and Virus Biology (Biodefense Research Section)

Postdoctoral Position – Immunology (Centre Hospitalier Universitaire Vaudois)

Postdoctoral Fellow – Innate Immunity (University of Connecticut Health Center)

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