Immunology of Infectious Disease News Volume 8.22 | Jun 10 2020

TOP STORY

A Single-Cell Atlas of the Peripheral Immune Response in Patients with Severe COVID-19

To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, scientists applied single-cell RNA sequencing to profile peripheral blood mononuclear cells from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. [Nat Med] Full Article

(Ranked by impact factor of the journal)

SARS-CoV-2

Expansion of Myeloid-Derived Suppressor Cells in Patients with Severe Coronavirus Disease (COVID-19)

Peripheral blood from 18 SARS-CoV-2-infected patients, nine with severe and nine with mild COVID-19 disease, was obtained at admission and analyzed for T-cell activation profile, myeloid-derived suppressor cells and cytokine profiles. Myeloid-derived suppressor cells functionality was tested in vitro. [Cell Death Differ] Full Article

The Inhibition of IL-2/IL-2R Gives Rise to CD8⁺ T Cell and Lymphocyte Decrease through JAK1-STAT5 in Critical Patients with COVID-19 Pneumonia

A total of 54 patients were enrolled and divided into three groups, among which 34 were common, 14 were severe, and six were critical. The constitution of peripheral blood mononuclear cells in patients was analyzed by CyTOF. [Cell Death Dis] Full Article

Sofosbuvir as a Potential Alternative to Treat the SARS-CoV-2 Epidemic

The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase showed that the residues that bound to the drug were present in the latter. [Sci Rep] Full Article

Crystal Structure of the SARS-CoV-2 Non-Structural Protein 9, Nsp9

Scientists sought to better characterize the SARS-CoV-2 Nsp9 and subsequently solve its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence. The SARS-CoV-2 Nsp9 structure revealed the high level of structural conservation within the Nsp9 family. [iScience] Abstract | Full Article | Graphical Abstract

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Interferon-Mediated Reprogramming of Membrane Cholesterol to Evade Bacterial Toxins

Researchers report that interferon (IFN) signals conveyed resistance to cholesterol-dependent cytolysin (CDC)-induced pores on macrophages and neutrophils. They traced IFN-mediated resistance to CDCs to the rapid modulation of a specific pool of cholesterol in the plasma membrane of macrophages without changes to total cholesterol levels. [Nat Immunol] Abstract

Reverse Engineering Synthetic Antiviral Amyloids

Investigators employed a synthetic biology approach in which they engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shared a homologous aggregation-prone fragment with a specific viral target protein. [Nat Commun] Full Article

Human Norovirus Targets Enteroendocrine Epithelial Cells in the Small Intestine

Abundant norovirus antigen and RNA were detected throughout the small intestinal tract in jejunal and ileal tissue from one pediatric intestinal transplant recipient with severe gastroenteritis. [Nat Commun] Full Article

VapBC22 Toxin-Antitoxin System from Mycobacterium tuberculosis Is Required for Pathogenesis and Modulation of Host Immune Response

Transcriptome analysis revealed that overexpression of VapC22 toxin in M. tuberculosis resulted in reduced levels of metabolic enzymes and increased levels of ribosomal proteins. Proteomics studies showed reduced expression of virulence-associated proteins and increased levels of cognate antitoxin, VapB22 in the ΔvapC22 mutant strain. [Sci Adv] Full Article

Neutrophil Swarming in Damaged Tissue Is Orchestrated by Connexins and Cooperative Calcium Alarm Signals

The authors showed that neutrophil swarms require mutual reinforcement of damage signaling at the wound core. New biosensors and live imaging in zebrafish revealed that neutrophil chemoattractant synthesis was triggered by a sustained calcium flux upon contact with necrotic tissue that requires sensing of the damage signal ATP. [Curr Biol] Full Article | Graphical Abstract

SUGT1 Controls Susceptibility to HIV-1 Infection by Stabilizing Microtubule Plus-Ends

Investigators found that suppressor of G2 allele of skp1 (SUGT1) determined the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. SUGT1 stabilized the microtubule plus-ends of host cells. [Cell Death Differ] Abstract

Slow Receptor Binding of the Noncytopathic HIV-2_UC1 Envs Is Balanced by Long-Lived Activation State and Efficient Fusion Activity

Scientists showed that HIV-2_UC1 Env interactions with the CD4 receptor exhibited slow association kinetics, whereas the dissociation kinetics was within the range of cytopathic strains. Despite the resulting 10- to 100-fold decrease in binding affinity, HIV-2_UC1 Envs exhibited long-lived activation state and efficient fusion activity. [Cell Rep] Full Article | Graphical Abstract

Fungal-Like Particles and Macrophage-Conditioned Medium Are Inflammatory Elicitors for 3T3-L1 Adipocytes

Researchers showed that heat-killed yeast induced an inflammatory response in adipocytes. Using fungal-like particles, namely laminarin-coated beads, they found that these particles triggered the expression of many key inflammatory genes in dose- and time-dependent fashions in adipocytes. [Sci Rep] Full Article

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Malaria Vaccines since 2000: Progress, Priorities, Products

Since the first trials published in 1997, RTS,S has been evaluated in a series of clinical trials culminating in Phase III testing, while testing of other pre-erythrocytic candidates, particularly whole sporozoite vaccines, has also increased. [npj Vaccines] Full Article

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

AbbVie, Harbor BioMed, Utrecht University and Erasmus Medical Center Announce Collaboration to Develop Monoclonal Antibody Therapy to Prevent and Treat COVID-19

AbbVie, Harbor BioMed, Utrecht University and Erasmus Medical Center announced they have entered into a collaboration to develop a novel antibody therapeutic to prevent and treat COVID-19, the pandemic respiratory disease caused by the SARS-CoV-2 virus. [AbbieVie (Business Wire, Inc.)] Press Release

INOVIO and IVI Partner with Seoul National University Hospital to Start Phase I/II Clinical Trial of INOVIO’s COVID-19 DNA Vaccine (INO-4800) in South Korea

INOVIO the International Vaccine Institute, and Seoul National University Hospital announced a partnership to start a Phase I/II clinical trial of INOVIO’s COVID-19 vaccine INO-4800 in South Korea at a signing ceremony [INOVIO] Press Release

Bavarian Nordic Announces Topline Results from Phase I Clinical Trial of Equine Encephalitis Virus Vaccine

Bavarian Nordic A/S announced topline results from the the first-in-human trial of MVA-BN^® WEV, a prophylactic vaccine candidate against three equine encephalitis viruses, for which there are currently no preventative vaccines available. [Bavarian Nordic A/S] Press Release

Junshi Biosciences Announces Dosing of First Healthy Volunteer in Phase I Clinical Study of SARS-CoV-2 Neutralizing Antibody JS016 in China

Junshi Biosciences announced that the first healthy volunteer has been dosed in the Phase I clinical study of JS016 at Huashan Hospital Affiliated to Fudan University in China. JS016 is the first SARS-CoV-2 neutralizing antibody to enter clinical trials in China. [Junshi Biosciences] Press Release

Elixirgen Therapeutics Concludes Pre-IND Meeting with FDA for Its COVID-19 Vaccine Candidate EXG-5003

Elixirgen Therapeutics, Inc. announced that it concluded on May 18 its pre-Investigational New Drug (pre-IND) meeting with the FDA for the company’s COVID-19 vaccine candidate, EXG-5003. EXG-5003 is a temperature-sensitive, intradermally-injected self-replicating RNA vaccine expressing the receptor binding domain of the SARS-CoV-2 spike protein. [Elixirgen Therapeutics, Inc.] Press Release

Three Big Studies Dim Hopes That Hydroxychloroquine Can Treat or Prevent COVID-19

Three large studies, two in people exposed to the virus and at risk of infection and the other in severely ill patients, show no benefit from the drug. Coming on top of earlier smaller trials with disappointing findings, the new results mean it’s time to move on, some scientists say, and end most of the trials still in progress. [ScienceInsider] Editorial

Coronavirus Rips through Dutch Mink Farms, Triggering Culls to Prevent Human Infections

In a sad sideshow to the COVID-19 pandemic, authorities in the Netherlands began to gas tens of thousands of mink on 6 June, most of them pups born only weeks ago. SARS-CoV-2 has attacked farms that raise the animals for fur, and the Dutch government worries infected mink could become a viral reservoir that could cause new outbreaks in humans. [ScienceInsider] Editorial

Lancet, NEJM Retract Surgisphere Studies on COVID-19 Patients

Two controversial studies of COVID-19 patients have been retracted after the authors failed to demonstrate that the data were reliable. The first study to be retracted, published May 22 in The Lancet, had found harmful effects associated with the antimalarial drug, hydroxychloroquine, but quickly drew fire after scientists raised questions about the massive database supposedly underpinning it, and about that database’s owner, Surgisphere Corporation. [The Scientist] Editorial

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NEW Professor – Experimental Medical Science in Immunology (Lund University)

Postdoctoral Fellow – Host-Viral Interactions (Thomas Jefferson Universtiy)

Postdoctoral Fellowship – Vaccinations (Brigham and Women’s Hospital)

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

Postdoctoral Fellow – Innate Lymphocytes and Influenza Pathogenesis (Oklahoma Medical Research Foundation)

Postdoctoral Fellow – Bacterial Infection (Seattle Children’s Research Institute)

Postdoctoral Researcher – Human Pathogenicity and Fungi (Hans Knöll Institute)

Research Fellow – Infectious Disease (The Lundquist Institute)

Director – Malaria Research (Johns Hopkins University)

Chair – Department of Microbiology and Immunology (Western University)

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