Immunology of Infectious Disease News Volume 7.26 | Jul 10 2019

TOP STORY

The Heme-Regulated Inhibitor Is a Cytosolic Sensor of Protein Misfolding that Controls Innate Immune Signaling

Investigators found that heme-regulated inhibitor was critical for signaling downstream of NOD1 and NOD2, two intracellular pattern recognition molecules of the nucleotide-binding domain leucine-rich repeat protein superfamily that detect bacterial peptidoglycan and induce pro-inflammatory NF-κB signaling. [Science] Abstract | Press Release

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CYRI/FAM49B Negatively Regulates RAC1-Driven Cytoskeletal Remodeling and Protects against Bacterial Infection

Researchers showed that CYRI binds to the small GTPase RAC1 through a conserved domain present in CYFIP proteins, which are known RAC1 effectors that stimulate actin polymerization. However, unlike CYFIP proteins, CYRI negatively regulated RAC1 signaling, thereby attenuating processes such as macropinocytosis, phagocytosis and cell migration. [Nat Microbiol] Abstract

Human Cytomegalovirus Evades Antibody-Mediated Immunity through Endoplasmic Reticulum-Associated Degradation of the FcRn Receptor

Scientists identified the mechanism by which human cytomegalovirus infection exploits an endoplasmic reticulum-associated degradation pathway through US11 to disable neonatal Fc receptor (FcRn) functions. [Nat Commun] Full Article | Press Release

SAMHD1 Modulates Early Steps during Human Cytomegalovirus Infection by Limiting NF-κB Activation

Investigators revealed a mechanism of human cytomegalovirus (HCMV) virus restriction by SAMHD1 and showed how SAMHD1 deficiency activates an innate immune pathway that paradoxically results in increased viral replication through transcriptional activation of the HCMV MIE gene promoter. [Cell Rep] Full Article | Graphical Abstract

EphA2 Is a Neutrophil Receptor for Candida albicans that Stimulates Antifungal Activity during Oropharyngeal Infection

The authors found that ephrin type-A receptor 2 (EphA2) on stromal cells is required for the accumulation of phagocytes in the oral mucosa of mice with oropharyngeal candidiasis (OPC). EphA2 on neutrophils was also central to host defense against OPC. [Cell Rep] Full Article | Graphical Abstract

T-bet Optimizes CD4 T-Cell Responses against Influenza through CXCR3-Dependent Lung Trafficking but Not Functional Programming

T-bet-deficient cells outcompeted wild-type cells to form lung-resident and circulating memory populations following viral clearance, and primed T-bet-deficient mice efficiently clear supralethal heterosubtypic influenza challenges even when depleted of CD8 T cells. [Mucosal Immunol] Abstract

Kynurenine 3-Monooxygenase Inhibition during Acute Simian Immunodeficiency Virus Infection Lowers PD-1 Expression and Improves Post-Combination Antiretroviral Therapy CD4⁺ T Cell Counts and Body Weight

Inhibition of kynurenine 3-monooxygenase in acute SIV infection disrupted the kynurenine pathway and prevented SIV-induced increases in downstream metabolites, improving clinical outcome as measured by both increased CD4⁺ T cell counts and body weight. [J Immunol] Abstract

Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Investigators tested the efficacy of convalescent plasma IgG hyperimmune product (ZIKV-IG) isolated from individuals with high neutralizing anti-Zika virus (ZIKV) titers as a therapeutic candidate against ZIKV infection using a model of ZIKV infection in Ifnar1^−/− mice. [Sci Rep] Full Article

Nucleic Acid Sensing Activates the Innate Cytosolic Surveillance Pathway and Promotes Parasite Survival in Visceral Leishmaniasis

Scientists demonstrated that cytosolic targeting of L.donovani DNA inhibits macrophage responsiveness to IFNɣ, through decreased MHC-II expression and lowered pSTAT1 levels, involving host three-prime repair exonuclease-1. [Sci Rep] Full Article

AgBR1 Antibodies Delay Lethal Aedes aegypti-Borne West Nile Virus Infection in Mice

Researchers showed that AgBR1 antibodies reduce the initial West Nile viral load and delay lethal infection after feeding by an infected Aedes aegypti mosquito. [npj Vaccines] Full Article

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Lessons from Next Generation Influenza Vaccines for Inflammatory Disease Therapies

Like influenza, there are different antigenic ‘strains’ and inflammatory T cell responses, Th1 or Th17, that drive each person’s disease. As such, next generation vaccine-like antigen specific therapies for inflammatory diseases can be developed but will need to be customized to the patient depending upon the antigen and T cell response that is driving the disease. [Int Immunopharmacol] Abstract

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Vaxart Enters into Research Collaboration with Janssen to Evaluate Oral Universal Influenza Vaccine

Vaxart, Inc. announced that it has entered into a research collaboration agreement with Janssen Vaccines & Prevention B.V. to evaluate Vaxart’s proprietary oral vaccine platform for the Janssen universal influenza vaccine program. [Vaxart, Inc. (Business Wire, Inc.)] Press Release

HIV Cure Program of American Gene Technologies Adds University of Maryland School of Medicine’s Institute of Human Virology as New Study Site to Support the Development of a Cell and Gene Therapy for HIV

American Gene Technologies selected the Institute of Human Virology at the University of Maryland School of Medicine as a new clinical site for its non-IND study, AGT-CS168, to collect clinical specimens from HIV positive individuals. [American Gene Technologies] Press Release

First Participant Enrolled in Second Cohort of BiondVax’s Pivotal, Clinical Efficacy, Phase III Universal Flu Vaccine Trial

BiondVax Pharmaceuticals Ltd. announced that the first participants in the second cohort of the pivotal, clinical efficacy, Phase III trial of the M-001 universal flu vaccine candidate have been successfully enrolled. [BiondVax Pharmaceuticals Ltd.] Press Release

Inovio Completes Enrollment of VGX-3100 Phase II Trial for the Treatment of HPV-Related Vulvar Dysplasia (VIN)

Inovio Pharmaceuticals, Inc. announced that it has completed enrollment in its Phase II trial with VGX-3100 in patients with precancerous lesions of the vulva or vulvar intraepithelial neoplasia. VGX-3100 is an immunotherapy that targets human papillomavirus (HPV) 16 and 18 and is being studied for the treatment of HPV-related precancerous lesions and the HPV infection that causes these lesions. [Inovio Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

RedHill Biopharma Announces FDA Acceptance of New Drug Application for Talicia

RedHill Biopharma Ltd. announced that the FDA has accepted for review the New Drug Application for Talicia^® for H. pylori infection. [RedHill Biopharma Ltd.] Press Release

Everyone Agrees This Superbug Is a Threat. Few Are Willing to Fund Research to Stop It

In the universe of scary drug-resistant pathogens that can kill, Candida auris is having a moment. The freaky fungus, which is behaving in ways scientists didn’t think fungi could act, has been garnering headlines because of its uncanny ability to resist multiple antifungal drugs and settle into hospital rooms so persistently it can take renovations to get rid of it. [STAT News] Editorial

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

As Visa Difficulties Persist, Scientists Push for Change

Individual researchers and science societies are finding solutions so colleagues around the globe can attend conferences, from remote presentations to relocating conferences. [The Scientist] Editorial

NEW 14^th World Congress on Inflammation Sydney 2019
September 15-19, 2019
Sydney, Australia

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NEW Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

NEW Postdoctoral Position – Mucosal Immunology (University of California, San Diego)

NEW PhD Studentship – Infection, Immunology and Global Health Research (Karolinska Institutet)

NEW Postdoctoral Position – Infectious Disease (National Institute of Health)

Postdoctoral Positions – Infectious Disease (The Laboratory for Molecular Infection Medicine)

Scientist – Infectious Diseases (Genentech, Inc.)

Research Associate – Immunology (Evotec)

Postdoctoral Position – Computational Biology (Helmholtz Centre for Infection Research)

Postdoctoral Position – Innate Immune Signaling in Spirochetal Diseases (UConn Health)

PhD Position – Chronic Viral Infections (Research Center for Molecular Medicine)

Postdoctoral Associate Positions – Infectious Diseases (University of Minnesota)

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