Immunology of Infectious Disease News Volume 8.09 | Mar 11 2020

TOP STORY

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Investigators showed that SARS-CoV-2 spike (S) used ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bound with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. They found that the SARS-CoV-2 S glycoprotein harbored a furin cleavage site at the boundary between the S₁/S₂ subunits, which was processed during biogenesis and set this virus apart from SARS-CoV and SARS-related CoVs. [Cell] Full Article | Graphical Abstract

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Mycobacterium tuberculosis Sulfolipid-1 Activates Nociceptive Neurons and Induces Cough

Researchers showed that an Mycobacterium tuberculosis (Mtb) organic extract activated nociceptive neurons in vitro and identified the Mtb glycolipid sulfolipid-1 (SL-1) as the nociceptive molecule. Mtb organic extracts from mutants lacking SL-1 synthesis could not activate neurons in vitro or induce cough in a guinea pig model. [Cell] Full Article | Graphical Abstract

Tuft-Cell-Derived Leukotrienes Drive Rapid Anti-Helminth Immunity in the Small Intestine but Are Dispensable for Anti-Protist Immunity

The authors showed that tuft cells secreted cysteinyl leukotrienes (cysLTs) to rapidly activate type 2 immunity following chemosensing of helminth infection. CysLTs cooperated with IL-25 to activate ILC2s, and tuft-cell-specific ablation of leukotriene synthesis attenuated type 2 immunity and delayed helminth clearance. [Immunity] Full Article | Graphical Abstract

Inflammasome-Mediated Antagonism of Type I Interferon Enhances Rickettsia Pathogenesis

Investigators report that the human pathogen Rickettsia parkeri was sensitive to type I interferons (IFN-I) and benefited from inflammasome-mediated host cell death that antagonized IFN-I. R. parkeri-induced cell death required the cytosolic lipopolysaccharide receptor caspase-11 and antagonized IFN-I production mediated by the DNA sensor cGAS. [Nat Microbiol] Abstract

TIGIT Limits Immune Pathology during Viral Infections

Scientists report that T cell immunoglobulin and ITIM domain (TIGIT) modulation effectively altered the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection, but did not affect virus control in vivo. Instead, TIGIT had an important effect in limiting immune pathology in peripheral organs by inducing IL-10. [Nat Commun] Full Article

Trib1 Regulates T Cell Differentiation during Chronic Infection by Restraining the Effector Program

Scientists identified Tribbles pseudokinase 1 (Trib1) as a central regulator of antiviral T cell immunity, where loss of Trib1 led to a sustained enrichment of effector-like KLRG1⁺ T cells, enhanced function, and improved viral control. [J Exp Med] Abstract

Lysosomal Degradation Products Induce Coxiella burnetii Virulence

A genome-wide small interfering RNA screen and reporter assay were used to identify host proteins required for Dot/Icm effector translocation. Significant, and independently validated, hits demonstrated the importance of multiple protein families required for endocytic trafficking of the C. burnetii-containing vacuole to the lysosome. [Proc Natl Acad Sci USA] Full Article

Disruption of Cellular Proteostasis by H1N1 Influenza a Virus Causes α-Synuclein Aggregation

Researchers investigated the effect of influenza virus (H1N1) strains on proteostasis of proteins associated with neurodegenerative diseases in Lund human mesencephalic dopaminergic cells in vitro and infection of Rag knockout mice in vivo. They demonstrated that acute H1N1 infection led to the formation of α–ynuclein and Disrupted-in-Schizophrenia 1 aggregates, but not of tau or TDP-43 aggregates, indicating a selective effect on proteostasis. [Proc Natl Acad Sci USA] Abstract

Activation of Meiotic Genes Mediates Ploidy Reduction during Cryptococcal Infection

The authors discovered that Cryptococcus cells polyploidized in response to genotoxic stresses that caused DNA double-strand breaks. Meiosis-specific genes were activated in Cryptococcus neoformans and contributed to ploidy reduction, both in vitro and during infection in mice. [Curr Biol] Full Article | Graphical Abstract

Protein S Protects against Allergic Bronchial Asthma by Modulating Th1/Th2 Balance

Investigators compared the development of allergen-associated bronchial asthma between wild type and protein S-overexpressing transgenic mice. Mice were sensitized and challenged with ovalbumin. They also evaluated the circulating levels of total and active protein S in patients with bronchial asthma and healthy controls. [Allergy] Abstract

Novel Elvitegravir Nanoformulation for Drug Delivery Across the Blood-Brain Barrier to Achieve HIV-1 Suppression in the CNS Macrophages

Investigators identified the clinical parameters including stability, biocompatibility, protein corona, cellular internalization pathway of elvitegravir (EVG) nanoformulation for its potential clinical translation. They further assessed the ability of this EVG nanoformulation to cross the in vitro blood brain barrier model and suppress the HIV-1 in macrophage cells. [Sci Rep] Full Article

The Activation of BAFF/APRIL System in Spleen and Lymph Nodes of Plasmodium falciparum Infected Patients

Researchers investigated the expression of B cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system components in lymphoid tissues from Plasmodium falciparum infected patients. Spleen and lymph node samples from 14 patients were collected at autopsy. [Sci Rep] Full Article

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Dysfunctional Immunometabolism in HIV Infection: Contributing Factors and Implications for Age-Related Comorbid Diseases

HIV infection alters immunometabolism by increasing reliance on aerobic glycolysis for energy and productive infection and repurposing oxidative phosphorylation machinery for immune cell proliferation and survival. Recent studies in people living with HIV with diabetes mellitus or cardiovascular disease have identified an association with elevated T cell and monocyte glucose metabolism, respectively. [Curr HIV/AIDS Rep] Abstract

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Vir Biotechnology Announces Research Collaboration with the National Institutes of Health Vaccine Research Center on Antibodies against Coronaviruses

Vir Biotechnology, Inc. announced a research collaboration agreement with the National Institutes of Health and the National Institute of Allergy and Infectious Diseases, Vaccine Research Center to advance characterization and development of human monoclonal antibodies against coronaviruses, including SARS-CoV-2, the virus that causes the disease COVID-19. [Vir Biotechnology, Inc.] Press Release

Emergent BioSolutions Signs Development and Manufacturing Agreement with Novavax for Experimental Vaccine Candidate for Coronavirus Disease

Emergent BioSolutions Inc. announced that it has entered into an agreement with Novavax, Inc. whereby Emergent will collaborate with Novavax, utilizing its molecule-to-market contract development and manufacturing services to support bringing into the clinic Novavax’s novel experimental vaccine candidate to protect against coronavirus disease. [Emergent BioSolutions Inc.] Press Release

CytoDyn Files IND and Protocol for Phase II Clinical Trial for Treatment of Coronavirus Patients with Leronlimab (PRO 140)

CytoDyn Inc. announced that the company has submitted an investigational new drug (IND) application to the FDA to conduct a Phase II clinical trial with leronlimab as a therapy for patients who experience respiratory complications as a result of contracting the coronavirus disease 2019. [CytoDyn Inc.] Press Release

Spero Therapeutics Receives FDA Orphan Drug Designation for SPR720 for the Treatment of Nontuberculous Mycobacterial (NTM) Infection

Spero Therapeutics, Inc. announced that the FDA has granted orphan drug designation for oral SPR720 for the treatment of NTM infection. [Spero Therapeutics, Inc.] Press Release

Novavax Awarded Funding from CEPI for COVID-19 Vaccine Development

Novavax, Inc. announced that the Coalition for Epidemic Preparedness (CEPI) awarded an initial funding of $4 million to support Novavax’ efforts to develop a COVID-19 vaccine. [Novavax, Inc.] Press Release

WHO Describes Outbreak as Pandemic

After weeks of resisting mounting pressure from scientists, politicians and others, the World Health Organization in Geneva has decided to describe the coronavirus outbreak as a pandemic. [Nature News] Editorial

NIH Official Suggests Large Gatherings Should Be Canceled Due to Coronavirus Outbreak

Anthony Fauci, the United State’s top infectious disease researcher, escalated his tone regarding the novel coronavirus outbreak during a congressional hearing, suggesting that large gatherings across the country should be canceled. [STAT News] Editorial

‘We’re Behind the Curve’: US Hospitals Confront the Challenges of Large-Scale Coronavirus Testing

In the United States COVID-19 cases are climbing at an alarming rate, and people who have received tests for the virus, SARS-CoV-2, remain few and far between. The White House coronavirus task force has insisted that early problems created by a faulty test distributed by the Centers for Disease Control and Prevention have been overcome and that the US government has increased production of functioning diagnostic kits. [SciencInsider] Editorial

NEW Scottish Structural Biology Meetings
April 3, 2020
Glasgow, United Kingdom

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NEW Research Fellow – Vaccine Research (Mayo Clinic)

NEW Postdoctoral Researcher – Respiratory Viruses (Flanders Institute for Biotechnology)

NEW Project Leader – Innate Immune Sensing (Helmholtz Centre for Infection Research)

Postdoctoral Research Fellowship – Molecular Infection Biology (Umeå University)

Postdoctoral Position – Bacterial Gastrointestinal Pathogens (Umeå University)

Postdoctoral Fellow/Research Scientist – Hepatitis Research (Nationwide Children’s Hospital)

Project Leader – Innate Immune Sensing and Bacterial RNA (Helmholtz Institute for RNA-Based Infection Research)

Department Chair – Microbiology and Immunology (Western University)

Postdoctoral Research – Cellular, Molecular, and Digital Medicine (CeMM Research Center for Molecular Medicine)

Postdoctoral Researcher – Microtubules in Viral Infection (Northwestern Feinberg School of Medicine)

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