Immunology of Infectious Disease News Volume 8.17 | May 6 2020

TOP STORY

Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza

Researchers demonstrated a CRISPR-Cas13-based strategy, PAC-MAN, for viral inhibition that could effectively degrade RNA from SARS-CoV-2 sequences and live influenza A virus in human lung epithelial cells. [Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

SARS-CoV-2

A Dynamic Immune Response Shapes COVID-19 Progression

Investigators conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients was highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for three to four weeks in all three patients. [Cell Host Microbe] Full Article | Graphical Abstract

A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells

The authors report that the cellular protease furin cleaved the spike protein at the S1/S2 site and that cleavage was essential for S-protein-mediated cell-cell fusion and entry into human lung cells. [Mol Cell] Full Article | Graphical Abstract | Press Release

A Human Monoclonal Antibody Blocking SARS-CoV-2 Infection

Researchers report a human monoclonal antibody that neutralized SARS-CoV-2 (and SARS-CoV) in cell culture. This cross-neutralizing antibody targeted a communal epitope on these viruses and may offer potential for prevention and treatment of COVID-19. [Nat Commun] Full Article

Effective Treatment of Severe COVID-19 Patients with Tocilizumab

Patients diagnosed as severe or critical COVID-19 were given tocilizumab in addition to routine therapy between 5 and 14 February 2020. The changes of clinical manifestations, computerized tomography scan image, and laboratory examinations were retrospectively analyzed. [Proc Natl Acad Sci USA] Full Article

Immune Environment Modulation in Pneumonia Patients Caused by Coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2

Scientists highlighted the key cytokines induced by coronavirus infections. They demonstrated that genes coding interleukins, chemokines, and interferons upsurged significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. [Aging (Albany NY)] Full Article

Deducing the N- and O- Glycosylation Profile of the Spike Protein of Novel Coronavirus SARS-CoV-2

Investigators report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. They characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain of spike protein subunit S1. [Glycobiology] Abstract | Full Article

The Anti-Influenza Virus Drug, Arbidol Is an Efficient Inhibitor of SARS-CoV-2 In Vitro

Researchers evaluated six currently available and licensed anti-influenza drugs against SARS-CoV-2. The drugs included arbidol, baloxavir, laninamivir, oseltamivir, peramivir, and zanamivir5,6. [Cell Discov] Full Article

MORE IMMUNOLOGY OF INFECTIOUS DISEASE

Mycobacterium tuberculosis Associated with Severe Tuberculosis Evades Cytosolic Surveillance Systems and Modulates IL-1β Production

Investigators studied 681 patients with pulmonary tuberculosis (TB) and showed that M. tuberculosis isolated from cases with mild disease consistently induced robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB did not do so. [Nat Commun] Full Article

Prodrugs of PKC Modulators Show Enhanced HIV Latency Reversal and an Expanded Therapeutic Window

The authors describe a strategy to address the problem of sustaining therapeutically meaningful levels while minimizing side effects based on latency reducing agent (LRA) prodrugs, designed for controllable release of the active LRA after a single injection. As intended, these prodrugs exhibit comparable or superiorin vitro activity relative to the parent compounds. [Proc Natl Acad Sci USA] Abstract

Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection

Researchers studied samples from 46 dengue virus (DENV)-naive and 43 DENV-immune patients with RT-PCR-confirmed Zika virus infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. [Cell Rep] Full Article | Graphical Abstract

Differential Expression of Interferon-Lambda Receptor 1 Splice Variants Determines the Magnitude of the Antiviral Response Induced by Interferon-Lambda 3 in Human Immune Cells

Scientists examined the regulation of type III interferons (IFN)-λR1 expression and measure the downstream effects of IFN-λ3 stimulation in primary human blood immune cells, compared with lung or liver epithelial cells. [PLoS Pathog] Full Article

Anti-Apoptotic Clone 11 Derived Peptides Induce In Vitro Death of CD4⁺ T Cells Susceptible to HIV-1 Infection

Investigators showed that expression of anti-apoptotic clone 11, an anti-apoptotic factor upregulated in many cancers, increased with progressive CD4⁺ T cell memory differentiation in association with the expression of cell cycle, activation and metabolism genes and correlated with susceptibility to HIV-1 infection. [J Virol] Abstract

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Pathological Inflammation in Patients with COVID-19: A Key Role for Monocytes and Macrophages

The authors describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19. [Nat Rev Immunol] Full Article

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AstraZeneca and Oxford University Announce Landmark Agreement for COVID-19 Vaccine

AstraZeneca and the University of Oxford announced an agreement for the global development and distribution of the University’s potential recombinant adenovirus vaccine aimed at preventing COVID-19 infection from SARS-CoV-2. [AstraZeneca] Press Release

GeoVax and Sino Biological Establish Exclusive Supply Agreement for Research Grade Bioreagents Related to SARS-Cov-2 (COVID-19) Vaccine Development

GeoVax Labs, Inc. announced that Beijing- and Philadelphia-based Sino Biological, Inc. will be its exclusive supplier of SARS-Cov-2 bioreagent research products. [GeoVax Labs, Inc.] Press Release

Santhera and Cold Spring Harbor Laboratory to Investigate Lonodelestat (POL6014) in COVID-19-Related Acute Respiratory Distress Syndrome (ARDS)

Santhera Pharmaceuticals has entered into a collaboration agreement with Cold Spring Harbor Laboratory to investigate the potential of lonodelestat, a potent inhibitor of human neutrophil elastase, as a therapeutic intervention for COVID-19-related ARDS. [Santhera Pharmaceuticals] Press Release

OSE Immunotherapeutics Announces COVID-19 Prophylactic Vaccine Program

OSE Immunotherapeutics announced that the company is committed to the fight against COVID-19. Its team of immunologists is actively working on the development of a prophylactic vaccine against the pandemic virus SARS-CoV-2. [OSE Immunotherapeutics] Press Release

FDA Approves 54 Emergency INDs for Leronlimab Treatment of Coronavirus – CytoDyn Requests Compassionate Use from FDA for COVID-19 Patients Not Eligible for Participation in Two Ongoing Clinical Trials in US

CytoDyn. Inc. announced that the company is expecting enrollment completion for its 75 patient, Phase II double blinded, placebo controlled, randomized study by the end of this month. [CytoDyn. Inc.] Press Release

Mounting Promises on COVID-19 Vaccines Are Fueling False Expectations, Experts Say

Vaccines to prevent Covid-19 infection are hurtling through development at speeds never before seen. But mounting promises that some vaccine may be available for emergency use as early as the autumn are fueling expectations that are simply unrealistic, experts warn. [STAT News] Editorial

‘It Will Not Be Easy.’ as Labs Begin to Reopen, Enormous Challenges Remain

One of the biggest challenges labs face is how to keep their members physically distanced to limit any potential spread of SARS-CoV-2. [ScienceInsider] Editorial

Coronavirus: Share Lessons on Lifting Lockdowns

Countries are starting to lift restrictions on movement, but there is little consensus on how this should be done. Sharing best practice is the way forward. [Nature News] Editorial

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NEW Postdoctroal Fellow – Bacterial Infection (Seattle Children’s Research Institute)

NEW Postdoctoral Researcher – Human Pathogenicity and Fungi (Hans Knöll Institute)

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)

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