Immunology of Infectious Disease News Volume 4.04 | Feb 3 2016

Glutamylation of the DNA Sensor cGAS Regulates Its Binding and Synthase Activity in Antiviral Immunity
Investigators found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. [Nat Immunol] Abstract

Dysbiosis-Induced IL-33 Contributes to Impaired Antiviral Immunity in the Genital Mucosa
Researchers demonstrated that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. [Proc Natl Acad Sci USA] Abstract

The Adhesion GPCR BAI1 Mediates Macrophage ROS Production and Microbicidal Activity against Gram-Negative Bacteria
Scientists found that brain-specific angiogenesis inhibitor 1 (BAI1) triggered the killing of the internalized bacteria by stimulating the production of reactive oxygen species. When engaged by bacteria, BAI1 activated Rac1 to stimulate the activity of the NADPH oxidase complex Nox2 in macrophages. [Sci Signal] Abstract

Combined Local and Systemic Immunization Is Essential for Durable T-Cell Mediated Heterosubtypic Immunity against Influenza A Virus
Adenoviral vectors expressing flu nucleoprotein have previously been found to induce short-term protection in mice. Researchers confirm that systemic immunization rapidly induced heterosubtypic protection predominantly mediated by CD8 T cells, but within three months clinical protection completely disappeared. [Sci Rep] Full Article

HIV

Actin Dynamics Regulates Dendritic Cell-Mediated Transfer of HIV-1 to T Cells
Scientists performed a shRNA screen of several hundred genes involved in organelle and membrane trafficking in immature human monocyte-derived dendritic cells. They identified TSPAN7 and DNM2, which control actin nucleation and stabilization, as having important and distinct roles in limiting HIV-1 endocytosis and in maintaining virus particles on dendrites, which is required for efficient transfer to T lymphocytes. [Cell]
Abstract | Graphical Abstract

Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression
Researchers found that human blood innate lymphoid cells (ILCs) were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy, but only if initiated during acute infection. [Immunity]
Abstract | Graphical Abstract | Press Release

Loss of Function of Intestinal IL-17 and IL-22 Producing Cells Contributes to Inflammation and Viral Persistence in SIV-Infected Rhesus Macaques
Investigators longitudinally determined the levels and functions of IL-17, IL-22 and IL-17/IL-22 producing CD4⁺ T-cells in blood, lymph node and colorectum of SIV-infected rhesus macaques, as well as how they recover during effective ART and are affected by ART interruption. [PLoS Pathog] Full Article

Prevention of SHIV Transmission by Topical IFN-β Treatment
The authors hypothesized that topically applied type 1 interferons might stimulate vaginal innate responses that could protect against HIV transmission. Vaginal administration of interferon (IFN)-β resulted in marked local changes in immune cell phenotype, increasing immune activation and HIV co-receptor expression, yet provided significant protection from simian/human immunodeficiency virus (SHIV) acquisition as IFN response genes were also upregulated. [Mucosal Immunol] Abstract

Potent In Vitro Antiviral Activity of Cistus incanus Extract against HIV and Filoviruses Targets Viral Envelope Proteins
Researchers demonstrated that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. [Sci Rep] Full Article | Press Release

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HIV Susceptibility of Human Antigen-Specific CD4 T Cells in AIDS Pathogenesis and Vaccine Response
The authors examine recent data regarding the HIV susceptibility of antigen-specific CD4 T cells induced during infection or HIV vaccination and discuss its potential impact on HIV acquisition risk posed by HIV vaccination. [Expert Rev Vaccines] Abstract

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MaxMind Gives $100K to GW Center for Neglected Tropical Diseases to Create Gene Drive to Eliminate Schistosomiasis
MaxMind has partnered with the George Washington University’s Research Center for Neglected Diseases of Poverty to end schistosomiasis through gene drive technology. MaxMind gave a $100K gift to support the establishment of a lab-based project that aims to eliminate schistosomiasis and the disease-causing parasites responsible for the infection, through a cutting-edge gene drive approach. [George Washington University] Press Release

Merck Receives FDA Approval of ZEPATIER™ (Elbasvir and Grazoprevir) for the Treatment of Chronic Hepatitis C Virus Genotype 1 or 4 Infection in Adults following Priority Review
Merck announced that the U.S. Food and Drug Administration (FDA) has approved ZEPATIER™ for the treatment of adult patients with chronic hepatitis C virus genotype (GT) 1 or GT4 infection, with or without ribavirin, following priority review by the FDA. [Merck & Co., Inc.] Press Release

Inovio Pharmaceuticals and GeneOne Life Science Initiate Patient Recruitment for MERS Vaccine Trial
Inovio Pharmaceuticals, Inc. announced the beginning of recruitment for its collaborative vaccine study for MERS (Middle East Respiratory Syndrome). Inovio and GeneOne Life Science Inc. are co-developing Inovio’s MERS vaccine in partnership with the Walter Reed Army Institute of Research, where the trial is being conducted. [Inovio Pharmaceuticals, Inc.] Press Release

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Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Global Medical Leader – Infectious Diseases (F. Hoffmann-La Roche)

Professor – Highly Infectious Diseases (Pennsylvania State University)

Research Associate – Bacterial Infection in the Context of Antimicrobial Resistance (Imperial College London)

Postdoctoral Position – Immunological Impact of Endogenous Retroviruses (The Francis Crick Institute)

Postdoctoral Position – Immunology (Indiana University School of Medicine)

Postdoctoral Position – Host-Microbial Interactions (University of Oxford)

Postdoctoral Position – Hantavirus and Inflammation Research (Karolinska Institutet)

Research Technician I – HIV Vaccine Trials (Fred Hutchinson Cancer Research Center)

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