Volume 3.40 | Oct 21

Immunology of Infectious Disease News 3.40 October 21, 2015
Immunology of Infectious Disease News
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Blood T Cells Are Resistant to HIV’s Primary Death Pathway
Scientists have discovered that blood-derived T cells are resistant to the chief cause of cell death in HIV infection. Instead, it is T cells in the lymphoid tissues that are most susceptible and whose death leads to the progression from HIV infection to AIDS. [Press release from the Gladstone Institutes discussing publication in Cell Host & Microbe] Press Release | Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
MicroRNAs Regulate the Immunometabolic Response to Viral Infection in the Liver
Researchers identified miR-130b and miR-185 as hepatic microRNAs whose expression is stimulated by 25‑hydroxycholesterol, an antiviral oxysterol secreted by interferon-stimulated macrophages and dendritic cells, during hepatitis C virus infection. [Nat Chem Biol] Abstract

Tuberculosis Is Associated with Expansion of a Motile, Permissive and Immunomodulatory CD16+ Monocyte Population via the IL-10/STAT3 Axis
In the context of active tuberculosis, investigators demonstrated that human monocytes are predisposed to differentiate towards an anti-inflammatory macrophage activation program characterized by the CD16+CD163+MerTK+pSTAT3+ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. [Cell Res] Abstract

Group A Streptococcal M1 Protein Sequesters Cathelicidin to Evade Innate Immune Killing
Researchers showed that the group A Streptococcus (GAS) surface-associated M1 protein sequesters and neutralizes LL-37 antimicrobial activity through its N-terminal domain. Exogenous M1 protein rescues M1-deficient GAS from killing by neutrophils and within neutrophil extracellular traps and neutralizes LL-37 chemotactic properties. [Cell Host Microbe] Abstract | Graphical Abstract | Press Release

Maternal CD4+ T Cells Protect against Severe Congenital Cytomegalovirus Disease in a Novel Nonhuman Primate Model of Placental Cytomegalovirus Transmission
Using a novel nonhuman primate model of congenital cytomegalovirus transmission, scientists demonstrated a critical role for maternal CD4+ T cells in the induction of protective maternal immune responses that prevent fetal demise. [Proc Natl Acad Sci USA] Abstract | Press Release


Activation and Lysis of Human CD4 Cells Latently Infected with HIV-1
An immunomodulatory protein was created that combines the specificity of a HIV-1 broadly neutralizing antibody with that of an antibody to the CD3 component of the T-cell receptor. CD3 engagement by the protein can stimulate T-cell activation that induces proviral gene expression in latently infected T cells. [Nat Commun] Full Article | Press Release

Follicular Regulatory T Cells Impair Follicular T Helper Cells in HIV and SIV Infection
Utilizing both human and rhesus macaque models, scientists showed the impact of HIV and SIV infection on follicular regulatory T cells (TFR) number and function. They found that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signaling, low apoptosis rates and the presence of regulatory dendritic cells. [Nat Commun] Full Article

CD4+ T Cell–Dependent and CD4+ T Cell–Independent Cytokine-Chemokine Network Changes in the Immune Responses of HIV-Infected Individuals
Researchers hypothesized that there were CD4+ T cell–dependent and CD4+ T cell–independent alterations in the immune responses of HIV-1+ individuals. To test this, they analyzed the secretion of cytokines and chemokines from stimulated peripheral blood mononuclear cell populations from HIV+ donors, healthy donors, and healthy donors with CD4+ T cells experimentally depleted. [Sci Signal] Abstract

The Mixed Lineage Kinase-3 Inhibitor URMC-099 Improves Therapeutic Outcomes for Long-Acting Antiretroviral Therapy
Long-acting ritonavir-boosted atazanavir nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc−/− mice. [Nanomedicine] Abstract | Press Release

Genome Editing of CXCR4 by CRISPR/cas9 Confers Cells Resistant to HIV-1 Infection
Scientists showed that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to human immunodeficiency virus type 1 (HIV-1) resistance of human primary CD4+ T cells. [Sci Rep] Full Article

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Immune Activation in the Course of HIV-1 Infection: Causes, Phenotypes and Persistence under Therapy
The authors discuss the various causes of immune activation in HIV-1 infected organisms: the presence of the virus together with other microbes, eventually coming from the gut, CD4+ T cell lymphopenia, senescence and dysregulation of the immune system, and/or genetic factors. [HIV Med] Abstract

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IDRI, Sanofi Pasteur Team with Philanthropy to Develop New Model for Vaccine Development
In an effort to accelerate timelines and decrease development costs of life-saving vaccines, the Infectious Disease Research Institute (IDRI) and Sanofi Pasteur announced the establishment of the Global Health Vaccine Center of Innovation. This project is funded in part by a grant from the Bill & Melinda Gates Foundation. [Infectious Disease Research Institute] Press Release

Inovio and Partner Advance MERS Vaccine
GeneOne Life Science Inc., which partnered with Inovio Pharmaceuticals, Inc. to develop Inovio’s MERS vaccine (GLS-5300), announced the filing of an Investigational New Drug Application for GLS-5300 with the United States Food and Drug Administration. [Inovio Pharmaceuticals, Inc.] Press Release

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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 18th Bangkok International Symposium on HIV Medicine 2016
January 13-15, 2016
Bangkok, Thailand

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NEW Postdoctoral Fellow – Exogenous and Endogenous Retroviruses (The Francis Crick Institute)

Postdoctoral Position – Immune Responses in Influenza Virus Infection (National Institute of Allergy and Infectious Diseases)

Research Associate – Immune System Interactions with Pathogens (University of Glasgow)

Lab Aide I – Immune Responses to Herpes Simplex Virus (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Precision Vaccines (Boston Children’s Hospital)

Canadian Research Chair Tier 1 – Systems Immunology (University of Manitoba)

Postdoctoral Scientist – Membrane Structural Biology and Virus-Host Interactions (Harbin Institute of Technology)

Assistant Professor – Immunology (Erasmus University Medical Center)

Postdoctoral Scientist – Host-Pathogen Interactions (Cedars-Sinai)

Postdoctoral Position – Immunology and Virology (Herman B Wells Center for Pediatric Research)

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