Immunology of Infectious Disease News Volume 4.15 | Apr 20 2016

Constitutive Aryl Hydrocarbon Receptor Signaling Constrains Type I Interferon–Mediated Antiviral Innate Defense
Scientists demonstrated that constitutive aryl hydrocarbon receptor (AHR) signaling negatively regulates the type I interferon (IFN-I) response during infection with various types of virus. Virus-induced IFN-β production was enhanced in AHR-deficient cells and mice and resulted in restricted viral replication. [Nat Immunol] Abstract

RUNX2 Mediates Plasmacytoid Dendritic Cell Egress from the Bone Marrow and Controls Viral Immunity
The authors showed that RUNX2 plays an essential role in promoting plasmacytoid dendritic cells (pDCs) localization and function. RUNX2 is required for the appropriate expression of the integrin-mediated adhesion machinery, as well as for the down-modulation of the chemokine receptor CXCR4, which allows pDC egress into the circulation. [Cell Rep] Full Article | Graphical Abstract

MAIT Cells Reside in the Female Genital Mucosa and Are Biased towards IL-17 and IL-22 Production in Response to Bacterial Stimulation
Investigators found that mucosal-associated invariant T (MAIT) cells and MR1⁺ antigen-presenting cells were present in the upper and lower female genital tract (FGT), with distinct tissue localization of MAIT cells in endometrium vs. cervix. When stimulated with Escherichia coli, MAIT cells from the FGT displayed a bias towards interleukin (IL)-17 and IL-22 expression, whereas blood MAIT cells produced primarily IFN-γ, TNF, and Granzyme B. [Mucosal Immunol] Full Article

HIV

Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys
Researchers showed that HIV-1 can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. [Cell] Abstract | Graphical Abstract | Press Release

NLRX1 Sequesters STING to Negatively Regulate the Interferon Response, Thereby Facilitating the Replication of HIV-1 and DNA Viruses
Scientists found that NLRX1 depletion results in impaired nuclear import of HIV-1 DNA in human monocytic cells. Additionally, NLRX1 was observed to reduce type-I interferon and cytokines in response to HIV-1 reverse-transcribed DNA. [Cell Host Microbe] Abstract | Graphical Abstract | Press Release

Th17 Cells Are Preferentially Infected Very Early after Vaginal Transmission of SIV in Macaques
Working with the macaque simian immunodeficiency virus (SIV) vaginal challenge model, investigators developed methodology to identify discrete foci of SIV infection 48 hours after vaginal inoculation. Phenotyping infected cells revealed that SIV has a significant bias for infection of CCR6⁺ CD4⁺ T cells. [Cell Host Microbe] Abstract | Graphical Abstract | Press Release

Nuclear Envelope Protein SUN2 Promotes Cyclophilin-A-Dependent Steps of HIV Replication
Researchers identified related capsid mutants in HIV-1, HIV-2, and SIVmac that are restricted by cyclophilin A (CypA). They showed that wild-type HIV exploits SUN2 in primary CD4⁺ T cells as an essential host factor that is required for the positive effects of CypA on reverse transcription and infection. [Cell Rep]
Full Article | Graphical Abstract

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Experimental Models of Hepatitis B and C — New Insights and Progress
Scientists describe the important part that experimental models have played in the study of viral hepatitis and led to monumental advances in our understanding and treatment of these pathogens. Ongoing developments in experimental models are also described. [Nat Rev Gastroenterol Hepatol] Abstract

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Study Demonstrates Benefits of Existing Treatment for Hepatitis D Patients
New research showed that interferon alpha based therapies are effective in suppressing disease progression in a severe form of chronic viral hepatitis, hepatitis delta. [Press release from the European Association for the Study of the Liver (EASL; EurekAlert!) discussing research presented at The International Liver Congress™ 2016, Barcelona] Press Release

Phase II Data Show Treatment Efficacy in ‘Difficult-to-Cure’ Hepatitis C Patients
A hepatitis C (HCV) drug currently under investigation, ABT-493 and ABT-530, which is an all-oral once-daily antiviral treatment, helped HCV genotype 3 patients with heavily scarred livers and no previous treatment history to achieve a 100% sustained virologic response after receiving the treatment for 12 weeks. [Press release from the European Association for the Study of the Liver (EASL; EurekAlert!) discussing research presented at The International Liver Congress™ 2016, Barcelona] Press Release

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RedHill Biopharma Announces Positive FDA Meeting on RHB-105 Path to Approval and Planned Confirmatory Phase III Study for H. pylori Infection
RedHill Biopharma Ltd. announced that it has concluded a positive type B meeting with the U.S. Food and Drug Administration (FDA) regarding the path to marketing approval of RHB-105 and the planned confirmatory Phase III study. [RedHill Biopharma Ltd.] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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Scientist – Bioengineering (STEMCELL Technologies Inc.)

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

Postdoctoral Researcher – HIV Biology (Johns Hopkins University)

Postdoctoral Position – Hepatitis B Virus Infection (University of Strasbourg)

Postdoctoral Position – Dendritic Cells in Inflammation and Infection (Centre d’Immunologie de Marseille Luminy)

Postdoctoral Fellow – Immunology (Ragon Institute of MGH, MIT and Harvard)

Principal Investigators – Infectious Diseases (CCID)

Administrative Head – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

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

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