Immunology of Infectious Disease News Volume 5.13 | Apr 5 2017

TOP STORY

Pre-Existing Immunity to Dengue and West Nile Viruses May Cause Increased Risk in Zika-Infected

As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers have found. Their study may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America. [Press release from Icahn School of Medicine at Mount Sinai discussing online prepublication in Science] Press Release | Abstract | Video

(Ranked by impact factor of the journal)

RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation

Using a mouse model of West Nile virus (WNV) encephalitis, the authors showed that receptor-interacting protein kinase-3 (RIPK3) restricts WNV pathogenesis independently of cell death. Ripk3^−/− mice exhibited enhanced mortality compared to wild-type controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. [Cell] Abstract | Graphical Abstract

Anerobic Bacterial Fermentation Products Increase Tuberculosis Risk in Antiretroviral-Drug-Treated HIV Patients

Investigators tested whether short-chain fatty acids (SCFAs) contribute to poor tuberculosis (TB) control in a longitudinal cohort of antiretroviral therapy (ART)-treated HIV-infected South Africans. Increase in serum SCFAs was associated with increased TB susceptibility. SCFAs inhibited IFN-γ and IL-17A production in peripheral blood mononuclear cells from HIV-infected ART-treated individuals in response to Mycobacterium tuberculosis antigen stimulation. [Cell Host Microbe] Abstract | Graphical Abstract

Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity

Scientists developed a model for fungal-mediated inducible bronchus-associated lymphoid tissue (iBALT) formation, using infection with Pneumocystis that induces development of pulmonary lymphoid follicles. Pneumocystis-dependent iBALT structure formation and organization required CXCL13 signaling. [Cell Rep] Abstract | Graphical Abstract

Antibody-Dependent-Cellular-Cytotoxicity-Inducing Antibodies Significantly Affect the Post-Exposure Treatment of Ebola Virus Infection

Researchers generated an Ebola virus-glycoprotein-pseudotyped human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. [Sci Rep] Full Article

Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy

Scientists showed that vaccination with low Ag dose selectively primes CD4 T cells of higher functional avidity, whereas CD8 T cell functional avidity was unrelated to vaccine dose in mice. [J Immunol] Full Article

Adaptive Immune Responses to Zika Virus Are Important for Controlling Virus Infection and Preventing Infection in Brain and Testes

Although wild-type C57BL/6 mice mount cell-mediated and humoral adaptive immune responses to Zika virus, these responses were not required to prevent disease. However, when the type I IFN response of mice was suppressed, then the adaptive immune responses became critical. [J Immunol] Abstract

HIV

Proliferation of Latently Infected CD4⁺ T Cells Carrying Replication-Competent HIV-1: Potential Role in Latent Reservoir Dynamics

The authors showed that latently infected cells can proliferate in response to mitogens without producing virus, generating progeny cells that can release infectious virus. [J Exp Med] Full Article

Polyfunctional Natural Killer Cells with a Low Activation Profile in Response to Toll-Like Receptor 3 Activation in HIV-1-Exposed Seronegative Subjects

Researchers investigated the polyfunctional natural killer (NK) cell response to Toll-like receptor (TLR)3 activation in serodiscordant couples. Exposed seronegative subjects showed increased IFN-γ and CD107a expression in both NK subsets, CD56^bright and CD56^dim cells, in response to stimulation with a TLR3 agonist, while expression was impaired in the HIV-1-infected partners. [Sci Rep] Full Article

Intracellular HIV-1 RNA and CD4⁺ T Cell Activation in Patients Starting Antiretrovirals

Scientists assessed if the reduction in HIV-1 RNA in CD4⁺ T cells is correlated with the persistence of immune activation following early antiretroviral therapy. [AIDS] Abstract

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Host-Virus Interaction of Zika Virus in Modulating Disease Pathogenesis

The authors focus on host-pathogen interactions to better understand Zika virus pathogenesis. [J Neuroimmune Pharmacol] Abstract

Targeting TNF and TNF Receptor Pathway in HIV-1 Infection: From Immune Activation to Viral Reservoirs

The authors describe the intricate interplay between HIV-1 proteins and tumor necrosis factor-α (TNF)/TNF receptor (TNFR) signaling and how TNF/TNFR activation modulates HIV-1 replication and discuss new therapeutic approaches, especially anti-TNF therapy, that could control this pathway and ultimately favor the clearance of infected cells to cure HIV-infected patients. [Viruses] Full Article

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ABIVAX Initiates Clinical Trial (ABX464-005) to Evaluate the Effect of ABX464 on HIV-Reservoirs in HIV Patients

ABIVAX announced that the first patient has been enrolled, effectively launching the study, for which it has obtained regulatory and ethical clearance. This study in 24 HIV patients and 12 healthy volunteers will examine the pharmacokinetics of ABX464 in HIV cellular reservoirs. [ABIVAX] Press Release

Cidara Therapeutics Awarded $6.9 Million Grant from CARB-X to Advance Development of Its First Cloudbreak™ Antibiotic Immunotherapy

Cidara Therapeutics, Inc. announced that the company has received a grant for up to $6.9 million from CARB-X (Combating Antibiotic Resistant Bacteria Accelerator) to advance the development of its antibiotic immunotherapy, CD201, for the treatment of life-threatening multi-drug resistant Gram-negative bacterial infections. [Cidara Therapeutics, Inc.] Press Release

Brazilian Scientists Reeling as Federal Funds Slashed by Nearly Half

Brazilian scientists have been left horrified by a 44% slash to the federal science budget, announced by the country’s government. This will leave the Ministry of Science, Technology, Innovations and Communications with its lowest budget in at least 12 years at just 2.8 billion reais, equivalent to US$898 million — a 2.2 billion reais cut from the 5 billion reais of funding that the government had originally proposed for 2017. [Nature News] Editorial

Genetic Details of Controversial ‘Three-Parent Baby’ Revealed

When a US fertility clinic revealed last year that it had created a baby boy using a controversial technique that mixes DNA from three people, scientists were quick to raise the alarm. Some objected on ethical grounds, and others questioned the scientific claims made by the clinic’s leader, physician John Zhang. [Nature News] Editorial

Few U.S. Animal Inspections Are Being Posted

The Donald Trump administration appears to have reversed its decision to remove from public sight the results of past government inspections of animal research facilities. But getting hold of new inspection reports is proving to be another matter. An animal welfare researcher has found that only four reports have been posted during the first quarter of 2017. [ScienceInsider] Editorial

NEW Gordon Research Conferences: Malaria
July 2-7, 2017
Les Diablerets, Switzerland

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NEW Postdoctoral Positions – Functional Genomics of Virus-Host Interactions (University of Strasbourg)

Research Technologist – Cell Separation & Immunology (STEMCELL Technologies, Inc.)

Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Postdoctoral Fellow – Malaria (Wellcome Trust Sanger Institute)

Postdoctoral Researcher – Infection Biology (Leibniz Institute for Natural Product Research and Infection Biology)

Doctoral Researcher – Infection Biology (Leibniz Institute for Natural Product Research and Infection Biology)

Postdoctoral Fellow – Autophagy Viral Infection & Antiviral Immunity (AstraZeneca)

Lecturer – Infectious Diseases (Virology)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Postdoctoral Research Fellow – CAR T Cell Therapy for HIV Infection (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Viral Infection Modeling (Fred Hutchinson Cancer Research Center)

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

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