Volume 2.07 | Feb 26

Immunology of Infectious Disease News 2.07 February 26, 2014
Immunology of Infectious Disease News
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The PYRIN Domain-Only Protein POP3 Inhibits ALR Inflammasomes and Regulates Responses to Infection with DNA Viruses
Researchers identified the PYRIN domain-only protein POP3, which competes with ASC for recruitment to AIM2-like receptors (ALRs), as an inhibitor of DNA virus-induced activation of ALR inflammasomes in vivo. Data obtained with a mouse model with macrophage-specific POP3 expression emphasize the importance of the regulation of ALR inflammasomes in monocytes and macrophages. [Nat Immunol] Abstract
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Cytotoxic CD8+ T Cells Stimulate Hematopoietic Progenitors by Promoting Cytokine Release from Bone Marrow Mesenchymal Stromal Cells
Results indicate that during an acute viral infection, Cytotoxic CD8+ T cells (CTLs) indirectly modulate early multipotent hematopoietic progenitors via mesenchymal stromal cells in order to trigger the temporary activation of emergency myelopoiesis and promote clearance of the infection. [Cell Stem Cell]
| Graphical Abstract | Press Release

Antimicrobial Peptide LL-37 Promotes Bacterial Phagocytosis by Human Macrophages
Scientists investigated the effect of LL-37 on bacterial phagocytosis by macrophages and demonstrate that LL-37 enhances phagocytosis of IgG-opsonized Gram-negative and Gram-positive bacteria in a dose- and time-dependent manner by dTHP-1 cells. [J Leukoc Biol] Abstract

An Unbalanced PD-L1/CD86 Ratio in CD14++CD16+ Monocytes Is Correlated with HCV Viremia during Chronic HCV Infection
Researchers analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets-CD14++CD16, CD14++CD16+ and CD14+/dimCD16+-in chronic hepatitis C virus (HCV)-infected patients, HCV spontaneous resolvers and healthy controls, and they evaluated the possible link between HCV viremia and disease progression. [Cell Mol Immunol] Abstract

Building and Optimizing a Virus-Specific T Cell Receptor Library for Targeted Immunotherapy in Viral Infections
T cell receptor (TCR) gene therapy can reconstitute CD8 T cell immunity in chronic patients. The authors cloned ten virus-specific TCRs targeting five different viruses, causing chronic and acute infection. All ten TCR genetic constructs were optimized for expression using a P2A sequence, codon optimization and the addition of a non-native disulfide bond. [Sci Rep] Full Article


CD4+ Memory Stem Cells (TSCM) Are Infected by HIV-1 in a Manner Regulated in Part by SAMHD1 Expression
Whether CD4+ TSCM are infected by HIV was investigated using a combination HIV reporter virus system in vitro and by direct staining for HIV p24 antigen ex vivo. A proportion of TSCM were found to express the HIV coreceptors CCR5 and CXCR4 and were infected by HIV both in vitro and in vivo. [J Virol] Abstract

High Avidity CD8+ T Cells Efficiently Eliminate Motile HIV-Infected Targets and Execute a Locally Focused Program of Anti-Viral Function
Using a 3D in vitro model of tissue, researchers visualized dynamic interactions between HIV-infected or peptide-pulsed CD4+ T-cells and HIV-specific CD8+ T-cells. CTLs engaged motile HIV-infected targets, but ~50% of targets broke contact and escaped. [PLoS One] Full Article

Δ9-Tetrahydrocannabinol Treatment during Human Monocyte Differentiation Reduces Macrophage Susceptibility to HIV-1 Infection
Ex vivo studies were designed to investigate effects on HIV-1 infection in macrophages exposed to Δ9-tetrahydrocannabinol (THC) during or following differentiation. THC treatment of primary human monocytes during differentiation reduced HIV-1 infection of subsequent macrophages by replication competent or single cycle CCR5 using viruses. [J Neuroimmune Pharm] Abstract

SAHA (Vorinostat) Induces CDK9 Thr186 (T-Loop) Phosphorylation in Resting CD4+ T-Cells – Implications for Reactivation of Latent HIV
Investigators found that suberoylanilide hydroxyamic acid (SAHA) treatment of isolated resting CD4+ T-cells induced CDK9 Thr186 phosphorylation in six of eight healthy donors and increased Cyclin T1 expression in one donor; Thr186 phosphorylation is required for P-TEFb function. [AIDS Res Hum Retroviruses] Abstract

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Circadian Clock Proteins and Immunity
Studies highlight the extent to which the molecular clock, most notably the core clock proteins BMAL1, CLOCK, and REV-ERBα, control fundamental aspects of the immune response. [Immunity] Abstract

HCV and HIV Co-Infection: Mechanisms and Management
New insights have revealed multiple mechanisms by which HCV and HIV lead to accelerated disease progression, specifically that HIV infection increases HCV replication, augments HCV-induced hepatic inflammation, increases hepatocyte apoptosis, increases microbial translocation from the gut and leads to an impairment of HCV-specific immune responses. [Nat Rev Gastroenterol Hepatol] Abstract

Chagas Disease: The Challenge of Polyparasitism?
Polyparasitism or mixed/concurrent infections occur more often than not and contribute to the high degree of variability observed across both disease progression and the success of therapeutic interventions. A thorough understanding of the effects of polyparasitism on Chagas disease (CD) is essential for improving the likelihood of containing, treating, and eventually eliminating CD. [Trends Parasitol] Abstract

Visit our reviews page to see a complete list of reviews in the infectious disease research field.

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Unusual New HIV Drug Resistance Mechanism Revealed
For the more than one million people with HIV/AIDS in the United States, antiretroviral drugs such as efavirenz and other so-called non-nucleoside reverse transcriptase inhibitors (NNRTIs) in combination with other antiretrovirals can be a lifeline, because they slow the progress of viral infection, prolonging life. Unfortunately, studies have shown that these benefits themselves can be short-lived in the clinic: therapy with NNRTIs can lead to single mutations in the HIV genetic code – mutations that make the virus resistant to the drugs. Researchers now have a good idea why. [Press release from Newswise Inc. discussing research presented at the 58th Annual Biophysical Society Meeting, San Francisco] Press Release | Abstract

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UNC Receives More than $40 million for Global Clinical Trials Unit to Treat, Prevent HIV
The University of North Carolina at Chapel Hill has received a seven-year, more than $40 million award from the National Institutes of Health (NIH) for a clinical trials unit that will implement the scientific agendas of five NIH networks devoted to HIV/AIDS treatment, prevention and cure research. [The University of North Carolina at Chapel Hill] Press Release

Children’s Hospital Los Angeles Awarded $17 Million by NIH to Fund Clinical Research on HIV/AIDS
Grace Aldrovandi, MD, CM, principal investigator at The Saban Research Institute of Children’s Hospital Los Angeles, has been awarded $17 million by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH). The goal of this grant is to provide scientific leadership and infrastructure for laboratory testing as part of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network. [Business Wire] Press Release

Lupin Receives FDA Approval for Generic Mycobutin® Capsules
Pharma Major Lupin Limited (Lupin) announced that it has received final approval for its Rifabutin Capsules USP, 150 mg from the United States Food and Drugs Administration (FDA) to market a generic version of Pharmacia and Upjohn Company’s Mycobutin® Capsules 150 mg. [Pharma Major Lupin Limited] Press Release
National Institutes of Health (United States)

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)
NEW International Union of Microbiological Societies Congresses
July 27-August 1, 2014
Montreal, Canada

NEW The 2014 Innate Immunity Summit
November 10-12, 2014
London, United Kingdom

Visit our events page to see a complete list of events in the infectious disease community.
NEW PhD Position – HIV Infection (Karolinska Institutet)

Professor of Virology (Institute of Tropical Medicine)

Faculty Position – Vaccine Immunology (Cornell University)

Postdoctoral Research Scientist – HIV (French Agency for Research on HIV and Viral Hepatitis)

Postdoctoral Fellow – Immunology (Institut für Klinische Chemie und Pathobiochemie Klinikum rechts der Isar)

Assistant Professor – Viral Oncologist (University of Maryland School of Medicine)

Postdoctoral Scientist – Avian Viral Diseases (The Pirbright Institute)

Postdoctoral Position – Epigenetic Regulation of Interleukin-12 Family Members (Université Libre de Bruxelles)

Research Associate – Translational Immunology (Genentech, Inc.)

Associate Professor – B Cell Immunologist (Institute of Human Virology at the University of Maryland School of Medicine)

Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

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