Immunology of Infectious Disease News Volume 5.33 | Aug 23 2017

TOP STORY

Public Antibodies to Malaria Antigens Generated by Two LAIR1 Insertion Modalities

The authors revealed different modalities of LAIR1 insertion that lead to public and dominant antibodies against infected erythrocytes and suggest that insertion of templated DNA represents an additional mechanism of antibody diversification that can be selected in the immune response against pathogens and exploited for B cell engineering. [Nature] Abstract | Press Release

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Zika-Virus-Encoded NS2A Disrupts Mammalian Cortical Neurogenesis by Degrading Adherens Junction Proteins

By systematically introducing individual proteins encoded by Zika virus (ZIKV) into the embryonic mouse cortex, investigators showed that expression of ZIKV-NS2A, but not Dengue virus-NS2A, leads to reduced proliferation and premature differentiation of radial glial cells and aberrant positioning of newborn neurons. [Cell Stem Cell] Abstract | Graphical Abstract

Interferon-γ-Driven iNOS: A Molecular Pathway to Terminal Shock in Arenavirus Hemorrhagic Fever

Researchers used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus, a close relative of Lassa virus, to investigate the pathophysiology of arenavirus hemorrhagic fever. [Cell Host Microbe] Abstract | Graphical Abstract

Delta Inulin-Based Adjuvants Promote the Generation of Polyfunctional CD4⁺ T Cell Responses and Protection against Mycobacterium tuberculosis Infection

Advax^™ is a novel adjuvant based on delta inulin microparticles that enhances immunity with a minimal inflammatory profile and has entered human trials to protect against viral pathogens. The authors determined if Advax displays broad applicability against important human pathogens by assessing protective immunity against infection with M. tuberculosis. [Sci Rep] Full Article

Asian Zika Virus Strains Target CD14⁺ Blood Monocytes and Induce M2-Skewed Immunosuppression during Pregnancy

Using human blood infection, researchers identified CD14⁺ monocytes as the primary target for African- or Asian-lineage Zika virus (ZIKV) infection. When immunoprofiles of human blood infected with ZIKV were compared, a classical/intermediate monocyte-mediated M1-skewed inflammation by the African-lineage ZIKV infection was observed, in contrast to a non-classical monocyte-mediated M2-skewed immunosuppression by the Asian-lineage ZIKV infection. [Nat Microbiol] Abstract | Press Release

Zika Virus Activates De Novo and Cross-Reactive Memory B Cell Responses in Dengue-Experienced Donors

Scientists tracked the evolution of Zika virus-induced B cell responses in three dengue virus (DENV)-experienced donors. The acute antibody (plasmablast) responses were characterized by relatively high somatic hypermutation and a bias toward DENV binding and neutralization, implying the early activation of DENV clones. [Sci Immunol] Full Article

HIV

One-Domain CD4 Fused to Human Anti-CD16 Antibody Domain Mediates Effective Killing of HIV-1-Infected Cells

Investigators report the design, generation and characterization of bispecific killer cells engagers (BiKEs) which consist of CD16A binding human antibody domains fused through a flexible linker to an engineered one-domain soluble human CD4. In the presence of cells expressing HIV-1 envelope glycoproteins (Envs), these BiKEs activated specifically CD16A-expressing Jurkat T cells, degranulated natural killer cells, induced cytokine production and killed Env-expressing cells. [Sci Rep] Full Article

NK Cells of HIV-1-Infected Patients with Poor CD4⁺ T-Cell Reconstitution Despite Suppressive HAART Show Reduced IFN-γ Production and High Frequency of Autoreactive CD56^bright Cells

HIV-1-infected patients failing to recover CD4⁺ T-cell count despite HAART are at increased risk of disease progression and death. To better understand the immunological non-responders (NR) status, researchers performed a comprehensive assessment of NK cells in NR patients as compared to immunologic responders. [Immunol Lett] Abstract

HDAC Inhibition Induces HIV-1 Protein and Enables Immune-Based Clearance Following Latency Reversal

Scientists applied enhanced methodology extending the sensitivity limits for the rapid detection of subfemtomolar HIV gag p24 capsid protein in CD4⁺ T cells from ART-suppressed HIV⁺ individuals, and they showed viral protein induction following treatment with latency-reversing agents. They demonstrated that clinical administration of histone deacetylase inhibitors induced HIV gag p24, and ex vivo stimulation produced sufficient viral antigen to elicit immune-mediated cell killing using anti-gp120/CD3 bispecific antibody. [JCI Insight] Full Article

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Mechanisms of Hepatitis B Virus Persistence

Hepatitis B virus (HBV) uses multiple pathways to harness host innate immunity to enhance its replication. It can also take advantage of the developing immune system and the not-yet-stabilized gut microbiota of young children to facilitate its persistence, and use maternal viral e antigen to educate immunity of the offspring to support its persistence after vertical transmission. The authors discuss knowledge gained from recent studies that pave the way for the development of new therapies for the treatment of chronic HBV infection, which has so far been very challenging. [Trends Microbiol] Abstract

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£2 Million Grant Aims to Tackle the Threat of Antimicrobial Resistance in Surgery

The international, multidisciplinary team, led by Alison Holmes, Professor of Infectious Diseases, has been awarded a £2 million grant from the Antimicrobial Resistance Cross Council Initiative supported by the seven research councils in partnership with other funders. The funding will be used to investigate how antibiotic use can be optimized in surgery to address antimicrobial resistance and minimize the burden of surgical infection. [Imperial College London] Press Release

Novartis and Medicines for Malaria Venture Launch Patient Trial in Africa for KAF156, a Novel Compound against Multidrug-Resistant Malaria

Novartis and Medicines for Malaria Venture launched a patient trial for KAF156, a next-generation antimalarial compound with the potential to treat drug-resistant strains of the malaria parasite. The trial will test the efficacy of KAF156 in combination with a new, improved formulation of the existing antimalarial lumefantrine. [Novartis] Press Release

AbbVie’s MAVIRET™ Approved by Health Canada for the Treatment of Chronic Hepatitis C in All Major Genotypes

AbbVie announced that Health Canada has granted approval for MAVIRET™, a once-daily, ribavirin-free treatment for adults with chronic hepatitis C virus infection across all major genotypes. [Abbvie] Press Release

Leaked Documents Expose Long-Standing Gender Tensions at Salk Institute

Senior female faculty at the Salk Institute for Biological Studies raise more than twice as much in National Institutes of Health funding for scientists working in their labs as their male counterparts, according to a 2016 internal report on “faculty issues” requested by leaders of the San Diego, California institution. Yet Salk leaders favored male scientists by granting them greater access to internal funds and other resources, the report implies, echoing gender discrimination lawsuits filed last month against the research center. [ScienceInsider] Editorial

A Bold Open-Access Push in Germany Could Change the Future of Academic Publishing

Over the past two years, more than 150 German libraries, universities, and research institutes have formed a united front trying to force academic publishers into a new way of doing business. Instead of buying subscriptions to specific journals, consortium members want to pay publishers an annual lump sum that covers publication costs of all papers whose first authors are at German institutions. Those papers would be freely available around the world; meanwhile, German institutions would receive access to all the publishers’ online content. [ScienceInsider] Editorial

NSF Reiterates Policy on Teaching Good Research Habits despite Its Limitations

The National Science Foundation (NSF) in Arlington, Virginia, has decided to double down on its implementation of a congressionally mandated policy aimed at reducing research misconduct among NSF-funded scientists, despite a new report that notes problems with the agency’s approach. [ScienceInsider] Editorial

NEW Keystone Symposia: Translational Systems Immunology
January 28-February 1, 2018
Snowbird, Utah, United States

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NEW Postdoctoral Scientist – Immunology/Microbial Pathogenesis (Nationwide Children’s Hospital)

Assistant or Associate Professor – Virology (University of Iowa)

Faculty Positions – Host-Pathogen Interactions (University of Chicago at Illinois)

Junior Professorship – Systems Biology of Human Parasites (Universität Hamburg)

Senior Bioinformatician – Malaria Genomics (Wellcome Trust Sanger Institute)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte. Ltd.)

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

Full Faculty Member – Immunology (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Cell Biology and Innate Immunity (Molecular Infection Medicine Sweden)

Lab Aide – Infectious Disease Sciences Program (Fred Hutchinson Cancer Research Center)

Staff Clinician Position – Laboratory of Clinical Infectious Diseases (National Institute of Allergy and Infectious Diseases)

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