Immunology of Infectious Disease News Volume 5.19 | May 17 2017

TOP STORY

Glycine Substitution at Helix-to-Coil Transitions Facilitates the Structural Determination of a Stabilized Subtype C HIV Envelope Glycoprotein

Based on targeted glycine substitutions in the HIV-1 envelope glycoprotein (Env) fusion machinery, scientists defined a general approach that disfavors helical transitions leading to post-fusion conformations, thereby favoring the pre-fusion state. They generated a stabilized, soluble clade C Env and determined its crystal structure at 3.9 Å. [Immunity] Full Article | Graphical Abstract

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Zinc Is a Potent and Specific Inhibitor of IFN-λ3 Signaling

Investigators showed that the rs12979860 CC genotype correlates with increased hepatic metallothionein expression through increased systemic zinc levels. Zinc interferes with lambda interferons-(IFN) λ3 binding to IFNL receptor 1, resulting in decreased antiviral activity and increased viral replication in vitro. [Nat Commun] Full Article

In Vitro Evolution of an Influenza Broadly Neutralizing Antibody Is Modulated by Hemagglutinin Receptor Specificity

Researchers explored the functional sequence space of broadly neutralizing antibody C05, which targets the receptor-binding site of influenza hemagglutinin (HA) via a long CDR H3. They combined saturation mutagenesis with yeast display to enrich for C05 variants of CDR H3 that bind to H1 and H3 HAs. The C05 variants evolved up to 20-fold higher affinity but increased specificity to each HA subtype used in the selection. [Nat Commun] Full Article

A Temporal Proteomic Map of Epstein-Barr Virus Lytic Replication in B Cells

The authors performed systematic quantitative analyses of temporal changes in host and Epstein-Barr virus (EBV) proteins during lytic replication to gain insights into virus-host interactions, using conditional Burkitt lymphoma models of type I and II EBV infection. They quantified profiles of >8,000 cellular and 69 EBV proteins, including >500 plasma membrane proteins, providing temporal views of the lytic B cell proteome and EBV virome. [Cell Rep] Full Article | Graphical Abstract

An Innate Defense Peptide BPIFA1/SPLUNC1 Restricts Influenza a Virus Infection

To determine a role in host defense against influenza A virus infection and to find the underlying defense mechanism, researchers developed transgenic mouse models that are deficient in bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell cultures, to investigate its antiviral properties. [Mucosal Immunol] Abstract

Both Haemagglutinin-Specific Antibody and T Cell Responses Induced by a Chimpanzee Adenoviral Vaccine Confer Protection against Influenza H7N9 Viral Challenge

Investigators developed a recombinant adenovirus-based vaccine, AdC68-H7HA, by cloning the H7N9 hemagglutinin gene into the chimpanzee adenoviral vector AdC68. The efficacy of AdC68-H7HA was evaluated in mice as well as guinea pigs. [Sci Rep] Full Article

Nitric Oxide Prevents a Pathogen-Permissive Granulocytic Inflammation during Tuberculosis

The authors report that nitric oxide primarily protects mice by repressing an interleukin-1- and 12/15-lipoxygenase-dependent neutrophil recruitment cascade that promotes bacterial replication. Using Mycobacterium tuberculosis mutants as indicators of the pathogen’s environment, they inferred that granulocytic inflammation generates a nutrient-replete niche that supports M. tuberculosis growth. [Nat Microbiol] Full Article

HIV

Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach

As the majority of infections world-wide are of the HIV-1 clade C subtype, researchers examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats. They detected superior germinal center formation and enhanced autologous neutralizing antibodies against the neutralization-resistant 16055 virus following inoculation of liposome-arrayed trimers. [Immunity] Abstract | Graphical Abstract

HIV-2 Infection Is Associated with Preserved GALT Homeostasis and Epithelial Integrity Despite Ongoing Mucosal Viral Replication

Scientists found viral replication in both sigmoid and ileum of asymptomatic HIV-2⁺ patients despite their undetectable viremia, accompanied by interferon-γ-producing CD8 T-cell expansion, irrespective of antiretroviral treatment. Nevertheless, there was no CD4 T-cell depletion, and Foxp3⁺ and IL-17- or IL-22-producing CD4 T-cell numbers were unaffected. [Mucosal Immunol] Abstract

Intranasal Drug Delivery of Small Interfering RNA Targeting Beclin1 Encapsulated with Polyethylenimine (PEI) in Mouse Brain to Achieve HIV Attenuation

The bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear PEI as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. [Sci Rep] Full Article

Further Characterization of the Bifunctional HIV Entry Inhibitor sCD4-FI_T45

Investigators analyzed the ability of soluble CD4 (sCD4)-fusion inhibitor (FI)_T45 to inhibit HIV envelope glycoprotein-mediated cell fusion and HIV entry of several primary isolates. sCD4-FI_T45 inhibited both cell fusion and HIV entry with remarkable antiviral activity. The mean 50% inhibitory concentrations for sCD4-FI_T45 were less than 0.2 μg/mL in both assays. [Mol Ther Nucleic Acids] Full Article

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Antiviral Goes Viral: Harnessing CRISPR/Cas9 to Combat Viruses in Humans

The authors review recent clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas)-based approaches to combat specific human viruses in humans and discuss challenges that need to be overcome before CRISPR/Cas9 may be used in the clinic as an antiviral strategy. [Trends Microbiol] Abstract

The Importance of Appropriate Initial Bacterial Colonization of the Intestine in Newborn, Child, and Adult Health

Colonizing intestinal bacteria are critical to the normal development of host defense. Disrupted colonization (dysbiosis) due to maternal dysbiosis, cesarean section delivery, use of perinatal antibiotics, or premature delivery may adversely affect the gut development of host defense and predispose to inflammation rather than to homeostasis, leading to increased susceptibility to disease later in life. [Pediatr Res] Abstract

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Investigational New Drug Application is Now Effective for Babesia Screening in Blood Donations Using Grifols Procleix Panther System in the US

Grifols announced that the U.S. Food and Drug Administration (FDA) has allowed collection and testing of blood samples for screening with Procleix Babesia assay under an Investigational New Drug study. [Grifols (PR Newswire Association LLC.)] Press Release

First Patient Transfused In Cerus’ Phase III Redes Study Evaluating Safety and Efficacy of the Intercept Red Blood Cell System

Cerus Corporation announced that the first patient has been transfused in Puerto Rico for the “INTERCEPT Blood System for Red Blood Cells in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections” clinical trial to assess the safety and efficacy of the INTERCEPT Blood System for red blood cells (RBCs) when compared to conventional RBCs in regions impacted by the Zika virus epidemic. [Cerus Corporation] Press Release

Ebola Vaccine Could Get First Real-World Test in Emerging Outbreak

An outbreak of the Ebola virus has emerged in the Democratic Republic of the Congo, the World Health Organization (WHO) said. Congolese authorities have reported nine suspected cases of Ebola infection in the past three weeks; the WHO has confirmed one, and tests are pending on others. [Nature News] Editorial

China’s Belt and Road Infrastructure Plan Also Includes Science

China’s plan to make massive investments in land and sea links with global trading partners also includes a little noticed commitment to support science and engineering, including the creation of dozens of new laboratories. [ScienceInsider] Editorial

Trump Officials Act to Tilt Federal Science Boards toward Industry

Critics say that changes to advisory groups at the Environmental Protection Agency and Department of Interior could restrict or paralyze them. [Nature News] Editorial

Biology Needs More Staff Scientists

Most research institutions are essentially collections of independent laboratories, each run by principal investigators who head a team of trainees. This scheme has ancient roots and a track record of success. But it is not the only way to do science. Indeed, for much of modern biomedical research, the traditional organization has become limiting. [Nature News] Editorial

NEW AACR-NCI-EORTC International Conference on Molecular Targets & Cancer Therapeutics
October 26-30, 2017
Philadelphia, United States

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

NEW Physician Scientist – Molecular Basis of Microbial Pathogenesis (Virginia Commonwealth University)

NEW Research Scientist – Microbiology / Molecular Biology (Day Zero Diagnostics)

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

NEW Research Technician I – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

Cell Biology Scientists – T Cells Responsive to Various Infectious Disease Targets (Immunocore)

Scientist I/II – Analytical Development (KBI Biopharma)

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

Associate Professorship – Virology (Charite – Universitatsmedizin Berlin)

Clinical Assistant II – Seattle Vaccine Trials Unit (Fred Hutchinson Cancer Research Center)

Assistant or Associate Member – Microbiome (Fred Hutchinson Cancer Research Center)

Junior Research Group Leader – Infection Biology (Julius-Maximilians Universitat Wurzburg)

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