Immunology of Infectious Disease News Volume 8.13 | Apr 8 2020

TOP STORY

A Highly Conserved Cryptic Epitope in the Receptor-Binding Domains of SARS-CoV-2 and SARS-CoV

Researchers determined the crystal structure of CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient, in complex with the receptor-binding domain of the SARS-CoV-2 spike protein to 3.1 Å. CR3022 targeted a highly conserved epitope, distal from the receptor-binding site, that enabled cross-reactive binding between SARS-CoV-2 and SARS-CoV. [Science] Full Article | Press Release

(Ranked by impact factor of the journal)

SARS-CoV-2

Infection and Rapid Transmission of SARS-CoV-2 in Ferrets

The authors report a ferret model of SARS-CoV-2 infection and transmission that recapitulated aspects of human disease. SARS-CoV-2-infected ferrets exhibited elevated body temperatures and virus replication. [Cell Host Microbe] Full Article | Graphical Abstract

Inhibition of SARS-CoV-2 (Previously 2019-nCoV) Infection by a Highly Potent Pan-Coronavirus Fusion Inhibitor Targeting Its Spike Protein that Harbors a High Capacity to Mediate Membrane Fusion

Investigators established a SARS-CoV-2 spike protein-mediated cell-cell fusion assay and found that SARS-CoV-2 showed a superior plasma membrane fusion capacity compared to that of SARS-CoV. They solved the X-ray crystal structure of six-helical bundle core of the HR1 and HR2 domains in the SARS-CoV-2 S protein S2 subunit, revealing that several mutated amino acid residues in the HR1 domain may be associated with enhanced interactions with the HR2 domain. [Cell Res] Full Article

Characterization of Spike Glycoprotein of SARS-CoV-2 on Virus Entry and Its Immune Cross-Reactivity with SARS-CoV

Using SARS-CoV-2 S protein pseudovirus system, researchers confirmed that human angiotensin converting enzyme 2 (hACE2) was the receptor for SARS-CoV-2, found that SARS-CoV-2 entered 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L were critical for entry, and that SARS-CoV-2 S protein was less stable than SARS-CoV S. [Nat Commun] Full Article

SARS-CoV-2 Receptor ACE2 and TMPRSS2 Are Primarily Expressed in Bronchial Transient Secretory Cells

Scientists investigated ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue and in cells derived from subsegmental bronchial branches by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 was expressed in both tissues, in the subsegmental bronchial branches ACE2 was predominantly expressed in a transient secretory cell type. [EMBO J] Abstract | Full Article

Structural Variations in Human ACE2 May Influence Its Binding with SARS-CoV-2 Spike Protein

Coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modeling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein respectively. [J Med Virol] Abstract | Full Article

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Bacteria-Induced Group 2 Innate Lymphoid Cells in the Stomach Provide Immune Protection through Induction of IgA

Microbes elicited IL-7 and IL-33 production in the stomach, which in turn triggered the propagation and activation of innate lymphoid cell 2 (ILC2). Stomach ILC2s were also rapidly induced following infection with Helicobacter pylori. [Immunity] Abstract

TNIK Signaling Imprints CD8⁺ T Cell Memory Formation Early after Priming

The authors analyzed the role of the TRAF2-/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8⁺ T cell fate during acute infection with lymphocytic choriomeningitis virus. [Nat Commun] Full Article

TLR9 Sensing of Self-DNA Controls Cell-Mediated Immunity to Listeria Infection via Rapid Conversion of Conventional CD4⁺ T Cells to T_reg

Investigators found that, depending on the size of initial dose, Listeria infection drove CD4⁺ T cells to act as T helper cells or induced rapid polyclonal conversion to immunosuppressive T_regs. Conversion to T^reg depended on the TLR9 and IL-12 pathways elicited by CD8α⁺ dendritic cell sensing of danger-associated neutrophil self-DNA. [Cell Rep] Full Article | Graphial Abstract

T Cell Factor 1 Suppresses CD103⁺ Lung Tissue-Resident Memory T Cell Development

Scientists found that T cell factor 1 was progressively decreased during lung tissue-resident memory CD8⁺ T (T_RM) cell formation. Abrogation of transforming growth factor β signaling was associated with a loss of CD103⁺ and reciprocal gain of T cell factor 1 cells among T_RM precursors in vivo. [Cell Rep] Full Article | Graphical Abstract

IFN-κ Suppresses the Replication of Influenza a Viruses through the IFNAR-MAPK-Fos-CHD6 Axis

Type I interferons (IFN-κ) efficiently suppressed the replication of various influenza viruses in cultured human lung cells, and chromodomain helicase DNA binding protein 6 (CHD6) was the major effector for the antiviral activity of IFN-κ, but not for that of IFN-α or IFN-β. [Sci Signal] Abstract

Combination Immunotherapy with Anti-PD-L1 Antibody and Depletion of Regulatory T Cells during Acute Viral Infections Results in Improved Virus Control but Lethal Immunopathology

Inhibitory receptors were blocked and regulatory T cells depleted in acutely Friend retrovirus-infected mice. Combination immunotherapy (CIT) resulted in a dramatic expansion of cytotoxic CD4⁺ and CD8⁺ T cells and a subsequent reduction in viral loads. Despite limited viral replication, mice developed fatal immunopathology after CIT. [PLoS Pathog] Abstract

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Breadth of Antibody Responses during Influenza Virus Infection and Vaccination

Inactivated vaccines are the best available countermeasure to induce effective antibodies against the emerged virus, but the response is narrow compared with potential breadth of virus infection. There is solid evidence to indicate that antibody responses to natural infection are relatively broad and exhibit quite different immunodominance patterns. [Trends Immunol] Abstract

Plasmodium vivax in Hematopoietic Niches: Hidden and Dangerous

Significant knowledge gaps remain in the understanding of host-parasite interactions, pathophysiology, and the implications for treatment and diagnosis of such a reservoir. Investigators discuss the current status of this emerging research field in the context of P. vivax. [Trends Parasitol] Abstract

The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease

The authors provide a model for the classification of macrophage activation syndrome (MAS) to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning adult respiratory distress syndrome from MAS. [Autoimmun Rev] Full Article

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STEMCELL Technologies Is an Essential Industry Partner for COVID-19 Research and Vaccine Development

Products made by STEMCELL Technologies are now being used in over 30 COVID-19 studies worldwide. These studies are focusing on areas ranging from diagnostics and treatments to vaccine development and future prevention. STEMCELL is playing a crucial role in COVID-19 research by providing cutting-edge laboratory tools and reagents as well as through close collaborations with scientists. [STEMCELL Technologies, Inc.] Press Release

Mateon Achieves Milestone in Its Development of OT-101, a Phase III Clinical Drug Candidate, against COVID-19

Mateon Therapeutics, Inc. announced that Mateon has delivered the requisite testing results to Golden Mountain Partners confirming the applicability and potential use of OT-101 for the treatment of COVID-19. OT-101 exhibited potent activity against both COVID-19 and SARS with a robust safety index of >500. [Mateon Therapeutics, Inc.] Press Release

FDA Clears CytoDyn’s Phase II Randomized Trial to Treat Mild-to-Moderately Ill Coronavirus Patients with Leronlimab; Enrollment to Begin Immediately

CytoDyn, Inc. announced today that the FDA just provided clearance for initiation of a Phase II trial with CytoDyn’s leronlimab to treat COVID-19 patients with mild to moderate indications. [CytoDyn, Inc.] Press Release

Hope Biosciences Receives FDA Approval to Commence First Stem Cell Clinical Trial for Protection Against COVID-19

Hope Biosciences announced that FDA has approved a Phase II clinical trial evaluating efficacy and safety of Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells to provide immune support against COVID-19. [Hope Biosciences] Press Release

McGill Researcher Awarded HFSP 2020 Grant Worth $1M USD

The International Human Frontier Science Program Organization (HFSP) has awarded Judith Mandl, Associate Professor, Department of Physiology, and her collaborators a prestigious HFSP 2020 Program Grant for their research into the properties of T-cells and their movements. [McGill Reporter] Press Release

Trials of Drugs to Prevent Coronavirus Infection Begin in Health Care Workers

Several trials are underway in preparation or underway that seek to use drugs for what is called pre-exposure prophylaxis, a strategy already widely used against HIV. The Bill & Melinda Gates Foundation is funding plans for another huge study that will test the same two drugs in Africa, North America, and Europe. [ScienceInsider] Editorial

Former FDA Leaders Decry Emergency Authorization of Malaria Drugs for Coronavirus

The recent FDA emergency use authorization for two malaria drugs to treat COVID-19, based on thin evidence of efficacy, has jeopardized research to learn the drugs’ real value against the pandemic coronavirus, say former agency executives under President Donald Trump and former President Barack Obama. [ScienceInsider] Editorial

COVID-19 Vaccine Frontrunners

Four vaccine candidates-two in the US, one in China, and one in the UK-have been approved for early testing in people. Several others are close on their heels. How the early candidates will perform, which will be advanced to later stages of clinical development, what safety issues might arise, and how a successful vaccine will be mass produced are among the questions that are now getting attention and funding. [The Scientist] Editorial

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NEW Postdoctoral Fellow – Mucosal Biology (University of Gothenburg)

NEW Group Leader – Anti-Microbial Resistance (Helmholtz Centre for Infection Research)

Professorship – Epidemiology in Occupational Medicine (Jena University Hospital)

Research Fellow – COVID-19 Virology (Queen’s University Belfast)

Postdoctoral Researcher – Microbiology of Mycobacterium tuberculosis (University of Oslo)

Research Fellow – Vaccine Research (Mayo Clinic)

Postdoctoral Researcher – Respiratory Viruses (Flanders Institute for Biotechnology)

Postdoctoral Research Fellowship – Molecular Infection Biology (Umeå University)

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

Department Chair – Microbiology and Immunology (Western University)

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