Immunology of Infectious Disease News Volume 4.31 | Aug 10 2016

TOP STORY

Proteasome Inhibition for Treatment of Leishmaniasis, Chagas Disease and Sleeping Sickness

Researchers describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Improving the Efficacy and Safety of Biologic Drugs with Tolerogenic Nanoparticles

Researchers demonstrated that poly(lactic-co-glycolic acid) nanoparticles carrying rapamycin, but not free rapamycin, are capable of inducing durable immunological tolerance to co-administered proteins that is characterized by the induction of tolerogenic dendritic cells, an increase in regulatory T cells, a reduction in B cell activation and germinal centre formation, and the inhibition of antigen-specific hypersensitivity reactions. [Nat Nanotechnol] Abstract | Press Release

Protective Efficacy of Multiple Vaccine Platforms against Zika Virus Challenge in Rhesus Monkeys

Investigators demonstrated that three different vaccine platforms protect against Zika virus challenge in rhesus monkeys. [Science] Abstract | Press Release

Inflammatory Monocytes and NK Cells Play a Crucial Role in DNAM-1-Dependent Control of Cytomegalovirus Infection

Human cytomegalovirus (HCMV) down-regulates poliovirus receptor (PVR) expression, but the significance of this viral function in vivo remains unknown. Investigators demonstrated that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation. [J Exp Med] Abstract

Toxoplasma gondii TgIST Co-Opts Host Chromatin Repressors Dampening STAT1-Dependent Gene Regulation and IFN-γ-Mediated Host Defenses

Researchers have identified TgIST (T. gondii inhibitor of STAT1 transcriptional activity) as a critical molecular switch that is secreted by intracellular parasites and traffics to the host cell nucleus where it inhibits STAT1-dependent proinflammatory gene expression. [J Exp Med] Abstract

Mycobacterial Acid Tolerance Enables Phagolysosomal Survival and Establishment of Tuberculous Infection In Vivo

The authors showed in mice and zebrafish that innate macrophages overcome mycobacterial lysosomal avoidance strategies to rapidly deliver a substantial proportion of infecting bacteria to phagolysosomes. [Cell Host Microbe] Full Article | Graphical Abstract

HIV

HIV-1 Uses Dynamic Capsid Pores to Import Nucleotides and Fuel Encapsidated DNA Synthesis

During the early stages of infection, the HIV-1 capsid protects viral components from cytosolic sensors and nucleases such as cGAS and TREX, respectively, while allowing access to nucleotides for efficient reverse transcription. The authors showed that each capsid hexamer has a size-selective pore bound by a ring of six arginine residues and a ‘molecular iris’ formed by the amino-terminal β-hairpin. [Nature] Abstract | Press Release

Defective Proviruses Rapidly Accumulate during Acute HIV-1 Infection

The dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Scientists showed that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early antiretroviral therapy is initiated. [Nat Med] Abstract | Press Release

Dendritic Cells from HIV Controllers Have Low Susceptibility to HIV-1 Infection In Vitro but High Capacity to Capture HIV-1 Particles

Investigators found that monocyte derived dendritic cells (MDDCs) from HIV controllers (HICs) are less permissive to HIV-1 infection than cells from healthy donors. In contrast MDDCs from HICs are particularly efficient at capturing HIV-1 particles when compared to cells from healthy donors or HIV-1 patients with suppressed viral load on antiretroviral treatment. [PLoS Pathog] Full Article

HIV-1 Tat Exacerbates Lipopolysaccharide-Induced Cytokine Release via TLR4 Signaling in the Enteric Nervous System

Scientists determined the interactive effects of the viral protein HIV-1 Tat and lipopolysaccharide on enteric neurons and glia. [Sci Rep] Full Article

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What Scales the T Cell Response?

The authors underscore temporal integration of digital T cell receptor (TCR) signaling as the basis for achieving scaled response by means of accumulating crucial mediators over time. They also discuss the role of temporally integrated crosstalk between TCR and IL2 signaling in mediating a scaled, coherent, collective response by T cells. [Trends Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

Three Johns Hopkins Public Health Researchers Win Zika Challenge Grants

Three teams from the Johns Hopkins Bloomberg School of Public Health will be awarded grants from U.S. Agency for International Development’s Combating Zika and Future Threats Grand Challenge, the agency announced. [Johns Hopkins Bloomberg School of Public Health] Press Release

National Institutes of Health Awards $9 Million Grant for Study on Health Disparities in HIV Prevention

A research team from Penn Nursing, the University of Michigan School of Nursing and Emory University’s Rollins School of Public Health has been awarded a $9 million grant from the National Institutes of Health to adapt and test a HIV prevention intervention for adolescent men who have sex with men. [University of Pennsylvania School of Nursing] Press Release

NIH Begins Testing Investigational Zika Vaccine in Humans

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has launched a clinical trial of a vaccine candidate intended to prevent Zika virus infection. The early-stage study will evaluate the experimental vaccine’s safety and ability to generate an immune system response in participants. [National Institute of Allergy and Infectious Diseases] Press Release

First Doses of Flublok^® Influenza Vaccine of 2016/17 Have Shipped

Protein Sciences Corporation announced that the FDA has approved and released the first lots of Flublok^® influenza vaccine for distribution this season. Doses have been shipped and healthcare professionals and pharmacies that have pre-ordered Flublok should receive the vaccine this week. [Protein Sciences Corporation (PR Newswire Association LLC.)] Press Release

IAVI Awarded NIH Contract to Expedite AIDS Vaccine Development

The International AIDS Vaccine Initiative (IAVI) has been awarded a new contract from the National Institute of Allergy and Infectious Diseases, part of the U.S. National Institutes of Health (NIH) to expedite the development of promising AIDS vaccine candidates. [The International AIDS Vaccine Initiative] Press Release

Luminex Corporation Receives FDA Emergency Use Authorization for Zika Virus Molecular Detection Assay Commercially Available xMAP^® MultiFLEX™ Zika RNA Assay

Luminex Corporation announced that it has received Emergency Use Authorization from the U.S. Food and Drug Administration (FDA) for a multiplex nucleic acid test designed to detect Zika virus RNA in potentially infected patients using their blood serum, plasma, or urine. [Luminex Corporation] Press Release

University of Maryland School of Medicine Is Once Again on Center Stage in Developing Zika Vaccine to Fight International Disease

As world leaders increasingly recognize the Zika virus as an international public health threat, the Center for Vaccine Development at the University of Maryland School of Medicine’s Institute for Global Health has been chosen as one of three study sites in a human safety trial of a new Zika vaccine. [University of Maryland School of Medicine] Press Release

The FDA Is Prohibited from Going Germline

A potentially renewable provision of the Consolidated Appropriation Act of 2016 forestalling the prospect of human germline modification was signed into law on December 18th, 2015. The provision has since been incorporated again into the House and Senate appropriation bills for the fiscal year. [ScienceInsider] Editorial

US Agency Lifts Ban on Funding Human–Animal Hybrids

Researchers in the United States will soon be able to resume creating chimera-based projects. [Nature News] Editorial

US Grants for Zebrafish Studies on the Rise

Zebrafish are the rising stars of model-organism research, an analysis of grants from the US National Institutes of Health shows. [Nature Trend Watch] Editorial | Article 1 | Article 2

NEW 2016 Australasian HIV & AIDS Conference
November 14-18, 2016
Adelaide, Australia

Visit our events page to see a complete list of events in the community.

NEW Faculty Position – Immunology (Vanderbilt University Medical Center)

NEW Postdoctoral Fellow – Mucosal Immunology (University of Utah)

NEW Research Chair – Immunology and Infectious Disease (University of Edinburgh)

NEW Scientist – Infectious Disease (Infectious Disease Research Institute)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

PhD Positions – Infection Biology and Immunology (ZIBI Graduate School)

Postdoctoral Research Fellow – Quantitative Infectious Disease Methods (Fred Hutchinson Cancer Research Center)

Postdoctoral or Research Fellow/Staff Scientist – Humoral Immune Response to HIV-1 (National Institute of Allergy and Infectious Diseases)

Senior Researcher – Epidemiology of Infectious Diseases (El Colegio de la Frontera Sur)

Postdoctoral Fellow – Infectious Disease (Metabiota)

Postdoctoral Fellow – Malaria Genetics (Wellcome Trust Sanger Institute)

Research in HIV-Host DNA Repair Interactions – HIV-1 Infection of Macrophages and Monocytes (Johns Hopkins University)

Two Postdoctoral Positions – Viral Hepatitis (Inserm)

Postdoctoral Research Fellow – Immune Response to Infection (Fred Hutchinson Cancer Research Center)

Principal Investigators – Infectious Diseases (CCID)

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