Immunology of Infectious Disease News Volume 8.16 | Apr 29 2020

TOP STORY

SARS-CoV-2 Entry Factors Are Highly Expressed in Nasal Epithelial Cells Together with Innate Immune Genes

Researchers co-detected transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes were co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. [Nat Med] Full Article

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SARS-CoV-2

Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients

The expression of pro-inflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. [Cell Host Microbe] Abstract | Full Article | Graphical Abstract

Neutralization of SARS-CoV-2 Spike Pseudotyped Virus by Recombinant ACE2-Ig

Investigators generated a recombinant protein by connecting the extracellular domain of human angiotensin-converting enzyme 2 (ACE2) to the Fc region of the human immunoglobulin IgG1. A fusion protein containing an ACE2 mutant with low catalytic activity was also used. [Nat Commun] Full Article

Profile of IgG and IgM Antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

The authors profiled the serological responses to SARS-CoV-2 nucleocapsid protein and spike glycoprotein. The majority of the patients developed robust antibody responses between 17 and 23 days after illness onset. [Clin Infect Dis] Abstract | Full Article

ACE2 Correlated with Immune Infiltration Serves as a Prognostic Biomarker in Endometrial Carcinoma and Renal Papillary Cell Carcinoma: Implication for COVID-19

The correlation between angiotensin-converting enzyme 2 (ACE2) and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. [Aging (Albany NY)] Full Article

Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Scientists report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with SARS-CoV-2. The observations of virus in neural tissue, in conjunction with clinical correlated of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement. [J Med Virol] Abstract | Full Article

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Neutrophil Swarming Delays the Growth of Clusters of Pathogenic Fungi

Researchers designed an assay for studying how myeloperoxidase or NADPH oxidase, and the release of neutrophil extracellular traps, work together and contribute to neutrophil’s ability to contain clusters of live Candida. [Nat Commun] Full Article

Linking Indirect Effects of Cytomegalovirus in Transplantation to Modulation of Monocyte Innate Immune Function

Pairing unbiased bulk and single cell transcriptomics with functional analyses, the authors demonstrated that human monocytes infected with cytomegalovirus did not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. [Sci Adv] Full Article

Complex Genetic Architecture Underlies Regulation of Influenza-A-Virus-Specific Antibody Responses in the Collaborative Cross

Scientists utilized the Collaborative Cross (CC), a mouse genetic reference population, to study genetic regulation of variation in antibody response following influenza A virus (IAV) infection. CC mice showed significant heritable variation in the magnitude, kinetics, and composition of IAV-specific antibody response. [Cell Rep] Full Article | Graphical Abstract

ADAR1 Facilitates KSHV Lytic Reactivation by Modulating the RLR-Dependent Signaling Pathway

Investigators report that adenosine deaminase acting on RNA 1 (ADAR1) was required for optimal Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic reactivation from latency. Knockdown of ADAR1 in KSHV latently infected cells inhibited viral gene transcription and viral replication during KSHV lytic reactivation. [Cell Rep] Full Article | Graphical Abstract

Ectopic Tcf1 Expression Instills a Stem-Like Program in Exhausted CD8⁺ T Cells to Enhance Viral and Tumor Immunity

Scientists showed that ectopic Tcf1 expression potently promoted the generation of exhausted CD8⁺ T-stem cells in both a chronic viral infection and pre-clinical tumor models. Tcf1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade, leading to enhanced viral and tumor control. [Cell Mol Immunol] Abstract

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The Trinity of COVID-19: Immunity, Inflammation and Intervention

The authors provide an overview of the pathophysiology of SARS-CoV-2 infection. They describe the interaction of SARS-CoV-2 with the immune system and the subsequent contribution of dysfunctional immune responses to disease progression. [Nat Rev Immunol] Full Article

Chronic Immune Activation in TB/HIV Co-Infection

Investigators build on data that the reactivation of latent tuberculosis (TB) infection during HIV co-infection is likely to be driven by the events of HIV replication and therefore highlight the need to have optimum translational interventions directed at reactivation due to co-infection. [Trends Microbiol] Abstract

Seek and Hide: The Manipulating Interplay of Measles Virus with the Innate Immune System

Measles virus, which causes long-lasting immunosuppression and immune-amnesia, primarily infects and replicates in innate and adaptive immune cells, such as dendritic cells, macrophages, T cells and B cells. [Curr Opin Virol] Abstract | Graphical Abstract

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Merck and Institute for Systems Biology Collaborate to Define Molecular Mechanisms of SARS-CoV-2 Infection and Identify Potential Prognostic Biomarkers

Merck announced a new research collaboration to investigate and define the molecular mechanisms of SARS-CoV-2 infection and COVID-19 and identify targets for medicines and vaccines. [Merck & Co., Inc.] Press Release

Gilead Announces Results from Phase III Trial of Investigational Antiviral Remdesivir in Patients with Severe COVID-19

Gilead Sciences, Inc. announced top-line results from the open-label, Phase III SIMPLE trial evaluating five-day and ten-day dosing durations of the investigational antiviral remdesivir in hospitalized patients with severe manifestations of COVID-19 disease. [Gilead Sciences, Inc.] Press Release

Moderna Announces IND Submitted to US FDA for Phase II Study of mRNA Vaccine (mRNA-1273) against Novel Coronavirus

Moderna, Inc. announced that it has submitted an Investigational New Drug (IND) application to the FDA for the company’s mRNA vaccine candidate against SARS-CoV-2 to evaluate mRNA-1273 in Phase II and late-stage studies if supported by safety data from the Phase I study led by the NIAID, part of the National Institutes of Health. [Moderna, Inc.] Press Release

ViiV Healthcare Announces £3 Million Global Fund to Research the Impact of COVID-19 on the HIV Community and Fill Gaps in Prevention, Treatment and Care during the Pandemic

ViiV Healthcare announced the creation of the Global HIV and COVID-19 Emergency Response Fund. The £3 million fund will make available critical financial resources for research projects to study the medical and scientific impact COVID-19 is having on people living with HIV and community-based grants to help address specific challenges to the HIV community created by the global pandemic. [ViiV Healthcare] Press Release

As COVID-19 Forces Conferences Online, Scientists Discover Upsides of Virtual Format

As the novel coronavirus outbreak shutters businesses and disrupts everyday life for billions around the globe, massive annual conferences and small society meetings alike have moved online. The new format poses numerous technical and organizational challenges, but it also offers opportunities- for reaching wider audiences, reducing the carbon footprint of meeting travel, and improving diversity and equity. [ScienceInsider] Editorial

NIH Announces $1.5 Billion, ‘Shark Tank’-Like Initiative to Accelerate COVID-19 Testing

The National Institutes of Health announced a new $1.5 billion initiative to rapidly develop coronavirus diagnostics, an effort it says will result in the deployment of “millions of tests per week” by late summer or fall of this year. [STAT News] Editorial

In light of COVID-19, many conferences are being cancelled or postponed. As such:

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NEW Research Fellow – Infectious Disease (The Lundquist Institute)

Director – Malaria Research (Johns Hopkins University)

Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Mucosal Biology (University of Gothenburg)

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)

Research Fellow – Vaccine Research (Mayo Clinic)

Postdoctoral Research Fellowship – Molecular Infection Biology (Umeå University)

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

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