Immunology of Infectious Disease News Volume 8.11 | Mar 25 2020

TOP STORY

Influenza Virus Z-RNAs Induce ZBP1-Mediated Necroptosis

Investigators showed that replicating Influenza A virus generated Z-RNAs, which activated ZBP1 in the nucleus of infected cells. ZBP1 then initiated RIPK3-mediated mixed lineage kinase domain-like pseudokinase activation in the nucleus, resulting in nuclear envelope disruption, leakage of DNA into the cytosol, and eventual necroptosis. [Cell] Abstract | Graphical Abstract

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Altered Immunity of Laboratory Mice in the Natural Environment Is Associated with Fungal Colonization

Investigators examined how colonization by microorganisms within the natural environment contributed to immune system maturation by releasing inbred laboratory mice into an outdoor enclosure. In addition to enhancing differentiation of T cell populations previously associated with pathogen exposure, outdoor release increased circulating granulocytes. [Cell Host Microbe] Abstract | Graphical Abstract

Rapid Expansion of Treg Cells Protects from Collateral Colitis following a Viral Trigger

Researchers showed that viral infection with LCMV resulted in type I IFN-dependent Treg cell loss that was rapidly compensated by the conversion and expansion of Vβ5⁺ conventional T cells into iTreg cells. Using Vβ5-deficient mice, they showed that these Vβ5⁺ iTreg cells were dispensable for limiting anti-viral immunity. [Nat Commun] Full Article

Clostridioides difficile Infection Damages Colonic Stem Cells via TcdB, Impairing Epithelial Repair and Recovery From Disease

Using the pathogen Clostridioides difficile, scientists showed that infection disrupted murine intestinal cellular organization and integrity deep into the epithelium, to expose the otherwise protected stem cell compartment, in a TcdB-mediated process. [Proc Natl Acad Sci USA] Full Article

Coronavirus Endoribonuclease Targets Viral Polyuridine Sequences to Evade Activating Host Sensors

The authors report that endoribonuclease (EndoU) cleaved the 5′-polyuridines from negative-sense viral RNA, termed PUN RNA, which was the product of polyA-templated RNA synthesis. Using a virus containing an EndoU catalytic-inactive mutation, they detected a higher abundance of PUN RNA in the cytoplasm compared to wild-type-infected cells. [Proc Natl Acad Sci USA] Full Article

Engineered Fluorescent E. coli Lysogens Allow Live-Cell Imaging of Functional Prophage Induction Triggered inside Macrophages

Researchers adopted a tripartite system where murine macrophages engulfed E. coli, which were lysogenic with an engineered bacteriophage λ, containing a fluorescent lysis reporter. Pre-induced prophages were capable of lysing the host bacterium and propagating infection to neighboring bacteria in the same phagosome. [Cell Syst] Abstract | Graphical Abstract

Route of Vaccine Administration Alters Antigen Trafficking but Not Innate or Adaptive Immunity

Investigators used rhesus macaques, physiologically relevant to humans, to identify the anatomical compartments and early immune processes engaged in the response to immunization via the two vaccine administration routes. Administration of fluorescently labeled HIV-1 envelope glycoprotein trimers displayed on liposomes enabled visualization of targeted cells and tissues. [Cell Rep] Full Article | Graphical Abstract

The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis

The authors demonstrated that myeloid cells from myeloid-restricted hypoxia-inducible factor-1 alpha (HIF-1α)-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms were more susceptible to L. donovani infection through increased lipogenesis. [Cell Rep] Full Article | Graphical Abstract

Virtual Memory CD8⁺ T Cells Restrain the Viral Reservoir in HIV-1-Infected Patients with Antiretroviral Therapy through Derepressing KIR-Mediated Inhibition

Researchers demonstrated that a population of unconventional CD45RA⁺, PanKIR⁺, and/or NKG2A⁺ virtual memory CD8⁺ T cells, which conferred rapid and robust protective immunity against pathogens, played an important role in restraining the HIV DNA reservoir in HIV-1-infected patients with effective ART. [Cell Mol Immunol] Abstract

Assessing the Impact of AGS-004, a Dendritic Cell-Based Immunotherapy, and Vorinostat on Persistent HIV-1 Infection

HIV⁺, stably treated participants in whom resting CD4⁺ T cell-associated HIV RNA increased after vorinostat (VOR) exposure ex vivo and in vivo, received four doses of AGS-004 every three weeks, followed by VOR every 72-hours for 30 days, and then the cycle repeated. [Sci Rep] Full Article

CRISPR-Based Gene Knockout Screens Reveal Deubiquitinases Involved in HIV-1 Latency in Two Jurkat Cell Models

To investigate host factors which promote HIV-1 latency, the authors conducted a genome-wide functional knockout screen using CRISPR-Cas9 in a HIV-1 latency cell line model. This screen identified IWS1, POLE3, POLR1B, PSMD1, and TGM2 as potential regulators of HIV-1 latency, of which PSMD1 and TMG2 could be confirmed pharmacologically. [Sci Rep] Full Article

Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection

Investigators showed that human cathelicidin antimicrobial peptide (AMP) LL-37 and engineered LL-37 AMPs inhibited the infection of recombinant virus pseudotyped with Ebola virus (EBOV) glycoprotein and the wild-type EBOV. [iScience] Abstract

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Immune-Microbiota Interplay and Colonization Resistance in Infection

The authors provide a mechanistic overview of the role of commensal microbes in modulating colonization resistance and pathogenic infections and means by which infectious agents may overcome such inhibition. [Mol Cell] Abstract

Inflammasome Activation in Response to Intracellular Protozoan Parasites

In recent years, many studies have addressed the role of inflammasomes during fungal, bacterial, viral, and parasitic diseases, revealing sophisticated aspects of the host–pathogen interaction. Investigators summarize recent advances on inflammasome activation in response to intracellular parasites, including Leishmania spp., Plasmodium spp., Trypanosoma cruzi, and Toxoplasma gondii. [Trends Parasitol] Abstract

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Canadian Biotechnology Company STEMCELL Technologies Provides Critical Support to Sequence the COVID-19 Virus, Accelerating Vaccine Development

Canada’s largest biotechnology company, Vancouver’s STEMCELL Technologies, has been making significant contributions to the fight against COVID-19. Human tissue culture systems developed by STEMCELL were used by researchers at China’s Center for Disease Control to grow lung airway cells that could successfully propagate the novel coronavirus SARS-CoV-2. [STEMCELL Technologies, Inc.] Press Release

CEL-SCI to Develop LEAPS COVID-19 Immunotherapy in Collaboration with University of Georgia Center for Vaccines and Immunology

CEL-SCI Corporatio announced it has signed a collaboration agreement with the University of Georgia’s Center for Vaccines and Immunology to develop LEAPS COVID-19 immunotherapy. CEL-SCI’s immunotherapy candidate aims to treat patients at highest risk of dying from COVID-19. [CEL-SCI Corporation] Press Release

Sorrento Collaborates with Mabpharm on Development and Commercialization of Ace-Mab™ to Potentially Treat COVID-19

Sorrento Therapeutics, Inc. announced it has entered into an exclusive license agreement with Mabpharm Limited for the clinical development and commercialization of the ACE-MAB fusion protein for the potential treatment of COVID-19, the disease caused by the SARS-CoV-2 virus. [Sorrento Therapeutics, Inc.] Press Release

Genentech Announces FDA Approval of Clinical Trial for Actemra to Treat Hospitalized Patients with Severe COVID-19 Pneumonia

Genentech announced the FDA has approved a randomized, double-blind, placebo-controlled Phase III clinical trial in collaboration with the Biomedical Advanced Research and Development Authority to evaluate the safety and efficacy of intravenous Actemra^® plus standard of care in hospitalized adult patients with severe COVID-19 pneumonia. [Genentech, Inc.] Press Release

US Food And Drug Administration Approves Epclusa^® (Sofosbuvir/Velpatasvir) for Children Ages 6 and Older or Weighing at Least 17 kg with Chronic Hepatitis C Infection

Gilead Sciences, Inc. announced that the FDA has approved a supplemental New Drug Application or Epclusa^® for the treatment of people with chronic hepatitis C infection (HCV) as young as six years of age or weighing at least 17 kg, regardless of HCV genotype or liver disease severity. [Gilead Sciences, Inc.] Press Release

ViiV Healthcare Announces First Global Regulatory Approval of CABENUVA; the First Complete, Long-Acting, Regimen for the Treatment of HIV

ViiV Healthcare announced that Health Canada has approved CABENUVA, the first and only once-monthly, complete long-acting regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in patients who are virologically stable and suppressed. [ViiV Healthcare (Business Wire, Inc.)] Press Release

Relatively Stable SARS-CoV-2 Genome Is Good News for a Vaccine

The small number of genetic differences between the original strain of the novel coronavirus from Wuhan and those currently circulating in the US population indicates that a vaccine may likely offer lasting immunity. [The Scientist] Editorial

Researchers Are Tracking Another Epidemic, Too—of Misinformation

When five researchers at the University of Washington, Seattle, launched the new Center for an Informed Public back in December 2019, they had no idea what was coming. The center aims to study how misinformation propagates and use the findings to “promote an informed society, and strengthen democratic discourse.” Now, just a few months later, the coronavirus pandemic is generating a tidal wave of information—some of it accurate, some not so much—that has saturated social and traditional media. [ScienceInsider] Editorial

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

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

NEW Postdoctoral Researcher – Tuberculosis (Karolina Instituet)

Postdoctoral Researcher – Drug Design against Coronavirus (Jülich Research Centre)

Research Fellow – Vaccine Research (Mayo Clinic)

Postdoctoral Researcher – Respiratory Viruses (Flanders Institute for Biotechnology)

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)

Department Chair – Microbiology and Immunology (Western University)

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