Immunology of Infectious Disease News Volume 4.42 | Oct 26 2016

TOP STORY

Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections

Scientists generated a large panel of orthopoxvirus-specific human monoclonal antibodies from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, cowpox, monkeypox, and variola virus and that are determinants of protection in murine challenge models. [Cell] Abstract | Graphical Abstract | Press Release

(Ranked by impact factor of the journal)

Cross-Regulation of Two Type I Interferon Signaling Pathways in Plasmacytoid Dendritic Cells Controls Anti-Malaria Immunity and Host Mortality

Researchers showed that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β in the serum and were resistant to lethal Plasmodium yoelii YM infection. [Immunity] Abstract | Graphical Abstract

Solute Carrier NTCP Regulates Innate Antiviral Immune Responses Targeting Hepatitis C Virus Infection of Hepatocytes

Investigators uncovered NTCP as a host factor regulating hepatitis C virus (HCV) infection. Using gain- and loss-of-function studies, they showed that NTCP mediates HCV infection of hepatocytes and is relevant for cell-to-cell transmission. [Cell Rep] Full Article | Graphical Abstract

The Tax-Inducible Actin-Bundling Protein Fascin Is Crucial for Release and Cell-to-Cell Transmission of Human T-Cell Leukemia Virus Type 1 (HTLV-1)

Repression of Fascin in HTLV-1-infected T-cells diminished virus release and gag p19 transfer to co-cultured T-cells. Spotting the mechanism, flow cytometry and automatic image analysis showed that Tax-induced T-cell conjugate formation occurred Fascin-independently. [PLoS Pathog] Full Article

Interferon-Driven Deletion of Antiviral B Cells at the Onset of Chronic Infection

Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus infection of mice, the authors documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. [Sci Immunol] Abstract

Type I Interferon Suppresses Virus-Specific B Cell Responses by Modulating CD8⁺ T Cell Differentiation

Using lymphocytic choriomeningitis virus (LCMV) as a model, researchers examined how a persistent viral infection can suppress neutralizing humoral immunity. By tracking the fate of virus-specific B cells in vivo, they report that LCMV-specific B cells were rapidly deleted within a few days of persistent infection, and this deletion was completely reversed by blockade of type I interferon signaling. [Sci Immunol] Abstract | Press Release

HIV

A Cas9 Ribonucleoprotein Platform for Functional Genetic Studies of HIV-Host Interactions in Primary Human T Cells

Scientists recently developed a method to edit the genome of primary CD4⁺ T cells by electroporation of CRISPR/Cas9 ribonucleoproteins. Here, they adapted this methodology to a high-throughput platform for the efficient, arrayed editing of candidate host factors. [Cell Rep] Full Article | Graphical Abstract | Press Release

Elevated Granzyme B⁺ B-Cell Level in SIV-Infection Correlate with Viral Load and Low CD4 T-Cell Count

This report demonstrates for the first time the existence of granzyme B-expressing⁺ B cells in SIV-infected rhesus macaques, which represent the most commonly used nonhuman primate model for HIV research. Similar to HIV patients, they found significantly higher frequencies of these cells in the blood of chronically SIV-infected rhesus monkeys compared with uninfected healthy ones. [Immunol Cell Biol] Full Article

Activation of HIV-1 Expression in Latently Infected CD4⁺ T Cells by the Small Molecule PKC412

The authors screened over 1,500 small molecules and kinase inhibitors and found that a small molecule, PKC412, can stimulate viral transcription and expression from the HIV-1 latently infected ACH2 cell line and primary resting CD4⁺ T cells. [Virol J] Full Article

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CD4⁺ and CD8⁺ T Cell Immunity to Dengue – Lessons for the Study of Zika Virus

The authors discuss the current knowledge of T cell immunity to dengue virus (DENV) and what it can teach us for the study of Zika virus (ZIKV). The extent of T cell cross-reactivity towards ZIKV of pre-existing DENV-specific memory T cells and its potential impact on protective immunity and/or immunopathology will also be discussed. [Immunology] Abstract

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Merck Highlights Ongoing Commitment to Fighting Infectious Diseases with More than 30 Data Presentations

Merck announced that researchers will provide more than 30 scientific data presentations on the company’s established and investigational infectious disease medicines and vaccines. [Press release from Merck discussing research presented at ID Week 2016, New Orleans] Press Release

FDA Approves Merck’s ZINPLAVA™ (Bezlotoxumab) to Reduce Recurrence of Clostridium difficile Infection (CDI) in Adult Patients Receiving Antibacterial Drug Treatment for CDI Who Are at High Risk of CDI Recurrence

Merck announced that the U.S. Food and Drug Administration (FDA) has approved ZINPLAVA™ Injection 25 mg/mL. ZINPLAVA is indicated to reduce recurrence of CDI in patients 18 years of age or older who are receiving antibacterial drug treatment of CDI and are at high risk for CDI recurrence. [Merck] Press Release

MicuRx Initiates Phase III Clinical Trial for MRX-I, a New Potent Oral Antibiotic against Gram-Positive Bacteria, Including MRSA

MicuRx Pharmaceuticals, Inc. announced that it has initiated patient enrollment in a pivotal Phase III study of MRX-I in China for the treatment of complicated skin and skin structure infections. [MicuRx Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

Scientific Challenges Loom for Canada’s Popular Prime Minister

Many in Canada’s science community say they are reserving judgement, waiting to see whether Trudeau can sustain his string of victories as he tackles some of country’s thorniest science-policy issues. [Nature News] Editorial

Review Finds Misconduct in Events Surrounding WHO Fetal Growth Study

For the first time in its 68-year history, the World Health Organization (WHO) has concluded that researchers are guilty of research misconduct. An independent review commissioned by WHO has found that “research ethics misconduct occurred” in a multimillion-dollar global study on fetal growth led by researchers at the University of Oxford in the United Kingdom. [ScienceInsider] Editorial

Two Major California Research Institutes Will Merge

One of the biggest nonprofit biomedical research outfits in the world is getting a new translational medicine research arm, aimed at speeding the conversion of basic research insights into novel medicines. Officials at the Scripps Research Institute announced that it will merge with the California Institute for Biomedical Research, which was launched in 2012 as a nonprofit version of a drug development company. [ScienceInsider] Editorial

To Save Money, NSF Requires University Cost-Sharing for Rotators

The National Science Foundation (NSF) has decided that universities should pay 10% of the salaries of faculty members working temporarily at the agency. NSF hopes the new policy will demonstrate its commitment to saving taxpayer dollars without alienating the academic community that it relies upon to stay on the cutting edge of basic science. [ScienceInsider] Editorial

NEW Keystone Symposium: Modeling Viral Infections and Immunity
May 1-4, 2017
Estes Park, United States

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NEW Postdoctoral Researcher – Infection and Immunity (University of Oxford)

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Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Research Specialist – Stem Cell Biology (University of Pittsburgh)

PhD Prize Studentships (University of Oxford)

Senior Postdoctoral Research Scientist – Genetics (University of Oxford)

Postdoctoral Position – Immunology (Klinikum der Universität München)

Faculty Positions – Immunology (Ohio State University)

Postdoctoral Positions – Mucosal, Innate and Adaptive Immunity (UT Southwestern Medical Center)

Faculty Position – Senior Immunologist (Fred Hutchinson Cancer Research Center)

Research Position – Immunotherapy Approach to Treat HIV Infection (California Institute of Technology)

Faculty Positions – Microbiology (University of Pennsylvania)

Postdoctoral Position – B Regulatory Cells (Inserm)

Faculty Position – Immunology (Vanderbilt University Medical Center)

Postdoctoral Fellow – Mucosal Immunology (University of Utah)

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

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