Immunology of Infectious Disease News Volume 8.14 | Apr 15 2020

TOP STORY

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

Investigators present the crystal structure of the C-terminal domain of SARS-CoV-2 spike protein in complex with human ACE2 (hACE2), which revealed a hACE2-binding mode similar overall to that observed for SARS-CoV. [Cell] Full Article | Graphical Abstract

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SARS-CoV-2

An Infectious cDNA Clone of SARS-CoV-2

Researchers report a reverse genetic system for SARS-CoV-2. Seven complimentary DNA (cDNA) fragments spanning the SARS-CoV-2 genome were assembled into a full-genome cDNA. RNA transcribed from the full-genome cDNA was highly infectious after electroporation into cells, producing 2.9 × 10⁶ plaque-forming unit/mL of virus. [Cell Host Microbe] Full Article | Graphical Abstract

Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense

The author showed that SARS-CoV-2 had the most extreme CpG deficiency in all known Betacoronavirus genomes. This suggested that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high zinc finger antiviral protein expression. [Mol Biol Evol] Abstract | Full Article

scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, a Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells

Scientists investigated the expression pattern of angiotensin-converting enzyme 2 (ACE2) in adult human testes at the level of single-cell transcriptomes. The results indicated that ACE2 was predominantly enriched in spermatogonia and Leydig and Sertoli cells. [Cells] Full Article

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Nanoparticle Uptake in a Spontaneous and Immunocompetent Woodchuck Liver Cancer Model

Researchers introduced a pre-clinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle-based in vivo experiments. Liver cancer development in these out-bred animals occured as a result of persistent viral infection, mimicking human hepatitis B virus-induced hepatocellular carcinoma development. [ACS Nano] Abstract | Full Article | Graphical Abstract

Passenger Mutations Confound Phenotypes of SARM1-Deficient Mice

Scientists generated knockout strains on the B6 background, confirming the role of SARM1 in axonal degeneration and WNV infection, but not in VSV or LACV infection, or in chemokine or Xaf1 expression. Sequence variation in proapoptotic Xaf1 between B6 and 129 resulted in coding changes and distinct splice variants, which may account for phenotypes previously attributed to SARM1. [Cell Rep] Full Article | Graphical Abstract

Diverse CD8 T Cell Responses to Viral Infection Revealed by the Collaborative Cross

The Collaborative Cross (CC), a large recombinant inbred panel of mice, is an ideal model in the pursuit for the high degree of genetic variation present, because it allows for assessment of genetic factors underlying unique phenotypes. The authors advanced the utility of the CC as a tool to analyze the immune response to viral infection. [Cell Rep] Full Article | Graphical Abstract

Apoptosis Characterization in Mononuclear Blood Leukocytes of HIV Patients during Dengue Acute Disease

Investigators found CD4/CD8 ratio inversion in most co-infected patients. CD4 T and CD8 T-cell subsets from Dengue virus (DENV) and DENV/HIV groups expressed low levels of anti-apoptotic protein Bcl-2. CD8 CD95 double positive cells frequency expressing low levels of Bcl-2 were significantly higher in these patients. [Sci Rep] Full Article

Polyfunctional HIV-1 Specific Response by CD8⁺ T Lymphocytes Expressing High Levels of CD300a

CD300a receptor expression was analysed by multiparametric flow cytometry on CD8⁺ T lymphocytes from HIV negative donors, naive HIV-1⁺ individuals and HIV-1⁺ subjects under suppressive combined antiretroviral therapy. HIV-1 specific CD8⁺ T cell response was studied by stimulating cells with HIV-1 derived peptides or with a Gag HIV-1 peptide. [Sci Rep] Full Article

ER Stress Regulates Immunosuppressive Function of Myeloid Derived Suppressor Cells in Leprosy that Can Be Overcome in the Presence of IFN-γ

Scientists found that HLA-DR^–CD33⁺CD15⁺ myeloid derived suppressor cells were increased in blood from patients with disseminated/progressive lepromatous leprosy and possessed T cell-suppressive activity as compared to self-limiting tuberculoid leprosy. [iScience] Abstract | Graphical Abstract

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COVID-19: Immunopathology and Its Implications for Therapy

Severe COVID-19 is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. [Nat Rev Immunol] Full Article

COVID-19: Risk for Cytokine Targeting in Chronic Inflammatory Diseases?

With sharply rising SARS-CoV-2 infection rates, patient groups characterized by an enhanced infection risk will be challenged by the virus. In this context, patients with chronic immune-mediated inflammatory diseases are of particular interest, as these diseases are characterized by an intrinsic immune dysfunction leading to inflammation that may enhance risk for severe infection. [Nat Rev Immunol] Full Article

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Sanofi and GSK to Join Forces in Unprecedented Vaccine Collaboration to Fight COVID-19

Sanofi and GlaxoSmithKline plc. (GSK) announced that they have signed a letter of intent to enter into a collaboration to develop an adjuvanted vaccine for COVID-19, using innovative technology from both companies, to help address the ongoing pandemic. [GlaxoSmithKline plc.] Press Release

Hope Biosciences Receives Second FDA Clearance for a Phase II Clinical Trial for Protection against COVID-19

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

Global Race to a COVID-19 Vaccine: Team at Harvard Plans to Launch Clinical Trial in Fall

In Dan Barouch’s lab, many researchers have not taken a day off since early January, and virtually all are working nearly seven days week to develop a vaccine that could help end the coronavirus pandemic. [The Harvard Gazette] Press Release

KD Pharma Group & SLA Pharma Initiate Clinical Trial for COVID-19

The KD Pharma Group and its partner, SLA Pharma, announced that its new drug candidate EPAspire™ is shortly entering clinical trials as a promising candidate to treat patients with symptoms of the novel coronavirus infection. [The KD Pharma Group] Press Release

ERC Launches Development Program for Novel Cell-Based Therapeutic and Prophylactic SARS-CoV-2 Vaccine

ERC Worldwide announced the launch of the company’s development program for its therapeutic and prophylactic vaccine against the new coronavirus SARS-CoV-2. The technology is based on ERC’s Gliovac/ERC1671 glioblastoma vaccine platform currently in an FDA approved clinical trial in the US. [ERC Worldwide (GlobeNewswire, Inc.)] Press Release

‘Short-Sighted.’ Health Experts Decry Trump’s Freeze on US Funding for WHO as World Fights Pandemic

President Donald Trump said he will suspend US funding to the WHO pending a 60- to 90-day investigation into how the agency has handled the response to the COVID-19 pandemic. Trump accused WHO of “severely mismanaging and covering up the spread of the coronavirus,” at a White House press conference in the Rose Garden. [ScienceInsider] Editorial

Global Infections Pass Two Million

The number of reported COVID-19 cases worldwide has passed two million, according to data compiled by researchers at Johns Hopkins University in Baltimore, Maryland. The milestone comes just two weeks after one million infections were recorded. The United States has the most cases – more than 600,000 – followed by Spain and Italy. [Nature News] Editorial

China Is Tightening Its Grip on Coronavirus Research

China’s government has started asserting tight control over COVID-19 research findings. Over the past two months, it appears to have quietly introduced policies that require scientists to get approval to publish – or publicize – their results, according to documents seen by Nature and some researchers. [Nature News] Editorial

First Saliva Test for COVID-19 Approved for Emergency Use by FDA

There are now more options for COVID-19 testing as the US FDA gave emergency use authorization on April 13 for a saliva-based test, providing an alternative to the swab testing currently performed. [The Scientist] Editorial

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NEW 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)

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)

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