Immunology of Infectious Disease News Volume 7.43 | Nov 6 2019

TOP STORY

Immunity to Commensal Papillomaviruses Protects against Skin Cancer

The authors showed that T cell immunity against commensal papillomaviruses suppressed skin cancer in immunocompetent hosts, and the loss of this immunity—rather than the oncogenic effect of human papilloma virus—caused the markedly increased risk of skin cancer in immunosuppressed patients. [Nature] Abstract

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Measles Virus Infection Diminishes Preexisting Antibodies that Offer Protection from Other Pathogens

Scientists studied 77 unvaccinated children before and two months after natural measles virus infection. Measles caused elimination of 11 to 73% of the antibody repertoire across individuals. [Science] Full Article | Press Release

Staphylococcus aureus Small Colony Variants Impair Host Immunity by Activating Host Cell Glycolysis and Inducing Necroptosis

Investigators found that both wild-type S. aureus and a ΔhemB small colony variant (SCV) prototype potently activated glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. [Nat Microbiol] Abstract

Bacterial Pathogens Hijack the Innate Immune Response by Activation of the Reverse Transsulfuration Pathway

Researchers showed that the enzyme cystathionine γ-lyase was induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase/MTOR and the transcription factor SP1. [mBio] Abstract

Development of Lentiviral Vectors for HIV-1 Gene Therapy with Vif-Resistant APOBEC3G

Lentiviral vectors that expressed A3G-D128K transduced CD34⁺ hematopoietic stem and progenitor cells with a high efficiency. A3G-D128K expression in T cell lines CEM, CEMSS, and PM1 potently inhibited spreading infection of several HIV-1 subtypes by C-to-U deamination leading to lethal G-to-A hypermutation and inhibition of reverse transcription. [Mol Ther Nucleic Acids] Abstract | Full Article | Graphical Abstract

Drug Discovery Platform Targeting M. tuberculosis with Human Embryonic Stem Cell-Derived Macrophages

Researchers report a modified protocol for generating homogeneous populations of macrophage-like cells from human embryonic stem cells. The induced macrophages, referred to as iMACs, presented similar transcriptomic profiles and characteristic immunological features of classical macrophages and were permissive to viral and bacterial infection, in particular M. tuberculosis. [Stem Cell Reports] Full Article | Graphical Abstract

Asian and African Lineage Zika Viruses Show Differential Replication and Innate Immune Responses in Human Dendritic Cells and Macrophages

Scientists characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells and macrophages. [Sci Rep] Full Article

Responses to Quadrivalent Influenza Vaccine Reveal Distinct Circulating CD4⁺CXCR5⁺ T Cell Subsets in Men Living with HIV

The authors showed that seroprotective antibody responses in serum and oral fluid correlated with cTFH activation and were equivalent in all three groups, irrespective of when antiretroviral therapy was started. These responses were attenuated in those reporting immunization with influenza vaccine in the preceding three years, independent of HIV infection. [Sci Rep] Full Article

Filovirus-Reactive Antibodies in Humans and Bats in Northeast India Imply Zoonotic Spillover

Investigators present evidence for prior exposure of bat harvesters and two resident fruit bat species to filovirus surface glycoproteins by screening sera in a multiplexed serological assay. Antibodies reactive to two antigenically distinct filoviruses were detected in human sera and to three individual filoviruses in bats in remote Northeast India. [PLoS Negl Trop Dis] Full Article | Press Release

Incomplete Genetic Reconstitution of B Cell Pools Contributes to Prolonged Immunosuppression after Measles

Using B cell receptor sequencing of human peripheral blood lymphocytes before and after measles virus (MeV) infection, researchers identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. [Sci Immunol] Full Article | Press Release

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The Regulation of CD4⁺ T Cells during Malaria

The authors describe mechanisms of CD4⁺ T cell activation during malaria and discuss the immunoregulatory mechanisms that develop to dampen their anti-parasitic and pathological functions. [Immunol Rev] Abstract

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Roche, Dicerna Launch Up-to-$1.67B Hepatitis B Collaboration

Roche will partner with Dicerna to develop and commercialize the Phase I chronic hepatitis B virus (HBV) candidate DCR-HBVS, as well as discover and develop additional HBV treatments, through a collaboration that could generate more than $1.67 billion for Dicerna. [Roche (Genetic Engineering & Biotechnology News)] Press Release

Altasciences Conducts Successful First-in-Human Trial for Acurx Pharmaceuticals’ Novel Antibiotic to Treat C. difficile Infection

On behalf of the sponsor, Acurx Pharmaceuticals, Altasciences completed the clinical conduct, data management, and SAS programming for ACX-362E, a novel, oral antibacterial agent for the treatment of Clostridioides difficile infection. [Altasciences] Press Release

FDA Approves Fluzone^® High-Dose Quadrivalent (Influenza Vaccine) for Adults 65 Years of Age and Older

The FDA has approved a supplemental Biologics License Application for Fluzone^® High-Dose Quadrivalent for use in adults 65 years of age and older. [Sanofi] Press Release

Second Ebola Vaccine Set to Be Used Soon in Democratic Republic of the Congo

The Democratic Republic of the Congo will begin using a second Ebola vaccine as early as next week, the company developing the experimental product, Johnson & Johnson (J&J), said Thursday. J&J announced it is donating enough of the product to vaccinate up to 500,000 people. [STAT News] Editorial

South Korea Clamps Down on Academics Attending ‘Weak’ Conferences

South Korea’s education ministry wants to stop academics from participating in conferences that it considers “weak” and of little academic value. The ministry announced on 17 October that it will require all universities to adopt measures to vet academics’ travel to overseas conferences so as to “prevent researchers from engaging in poor academic activities”. [Nature News] Editorial

Report Sketches Vision for UK Research after Brexit

An eagerly awaited external report, commissioned by the government, lays out research priorities and options if those relationships with Europe are severed. It calls for increased spending on R&D nationwide, a new research fellowship program, and larger chunks of money for universities to quickly target research opportunities. [ScienceInsider] Editorial

NEW Stromal Cells in Immunity and Disease
February 19-23, 2020
Victoria, British Columbia, Canada

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NEW Research Associate – Immunology (STEMCELL Technologies Inc.)

NEW Postdoctoral Associates – Virology and Vaccine Development (University of Minnesota)

Scientist – Infectious Disease (Infectious Disease Research Institute)

Postdoctoral Position – HIV (Tulane University)

Postdoctoral Position/PhD Student – Infectious Diseases, Host-Pathogen Interactions and Immunology (Purdue University)

Postdoctoral Associate – Lung Inflammation (The University of Georgia)

Postdoctoral Scientist – Flavivirus Infection (Pasteur Institute of Cambodia)

Assistant/Associate Professor – Immunology (University of Massachusetts)

Faculty Position – Life Sciences (University of Michigan)

Staff Clinician – Malaria Immunology and Vaccinology (The National Institute of Allergy and Infectious Diseases)

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