Immunology of Infectious Disease News Volume 4.49 | Dec 14 2016

TOP STORY

Receptor Usage Dictates HIV-1 Restriction by Human TRIM5α in Dendritic Cell Subsets

Researchers showed that human E3-ubiquitin ligase tri-partite-containing motif 5α (TRIM5α) potently restricts HIV-1 infection of Langerhans cells but not of subepithelial dendritic cell (DC)-SIGN⁺ DCs. [Nature] Abstract

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Molecular Determinants of Human Neutralizing Antibodies Isolated from a Patient Infected with Zika Virus

Investigators report the isolation of 13 specific human monoclonal antibodies from a single patient infected with Zika virus (ZIKV). Two of the isolated antibodies demonstrated potent ZIKV-specific neutralization in vitro without binding or neutralizing activity against strains 1 to 4 of dengue virus, the closest relative to ZIKV. [Sci Transl Med] Abstract

Expression of KIR2DS1 by Decidual Natural Killer Cells Increases Their Ability to Control Placental HCMV Infection

Scientists demonstrated that killer cell Ig-like receptor 2DS1 (KIR2DS1)⁺ decidual natural killer cells (dNK) acquired higher cytotoxic function than KIR2DS1⁻ dNK when exposed to human cytomegalovirus (HCMV)-infected decidual stromal cells (DSC), particularly when DSCs express HLA-C2. Furthermore, dNK were unable to degranulate or secrete cytokines in response to HCMV-infected primary fetal extravillous trophoblasts. [Proc Natl Acad Sci USA] Abstract

PD-1/PD-L Pathway Inhibits M.tb-Specific CD4⁺ T-Cell Functions and Phagocytosis of Macrophages in Active Tuberculosis

Researchers conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis patients and 16 healthy controls, were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes. [Sci Rep] Full Article

NKp30⁺ NK Cells Are Associated with HBV Control during Pegylated-Interferon-Alpha-2b Therapy of Chronic Hepatitis B

Investigators found that the frequency and absolute number of NKp30⁺ natural killer (NK) cells increased markedly, accompanied by enhanced CD107a and IFN-γ production, during Peg-IFN-α-2b monotherapy or combination therapy with adefovir dipivoxil in patients with CHB, especially in responders. [Sci Rep] Full Article

Rapid Profiling of RSV Antibody Repertoires from the Memory B Cells of Naturally Infected Adult Donors

Scientists comprehensively profiled the human antibody response to respiratory syncytial virus (RSV) F by isolating and characterizing 364 RSV F–specific monoclonal antibodies from the memory B cells of three healthy adult donors. In all donors, the antibody response to RSV F was composed of a broad diversity of clones that targeted several antigenic sites. [Sci Immunol] Abstract | Press Release

The TCF1-Bcl6 Axis Counteracts Type I Interferon to Repress Exhaustion and Maintain T Cell Stemness

Using chronic infection with lymphocytic choriomeningitis virus clone 13 and tumor samples, the authors demonstrated that CD8 T cells differentiate into a less exhausted T cell factor 1 (TCF1)^high and a more exhausted TCF1^low population. Virus-specific TCF1^high CD8 T cells, which resemble T follicular helper cells, persist and recall better than do TCF1^low cells and act as progenitor cells to replenish TCF1^low cells. [Sci Immunol] Abstract

HIV

Blocking Type I Interferon Signaling Enhances T Cell Recovery and Reduces HIV-1 Reservoirs

Researchers report studies using a monoclonal antibody to block interferon-α/β receptor signaling in humanized mice (hu-mice) that were persistently infected with HIV-1. They discovered that effective combined antiretroviral therapy restored the number of human immune cells in HIV-1–infected hu-mice but did not rescue their immune hyperactivation and dysfunction. [J Clin Invest] Full Article | Press Release

Targeting Type I Interferon–Mediated Activation Restores Immune Function in Chronic HIV Infection

Using HIV-infected humanized mice, investigators demonstrated that in vivo blockade of type I interferon signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. [J Clin Invest] Full Article | Press Release

Systemic Elevation of Proinflammatory Interleukin 18 in HIV/HCV Coinfection versus HIV or HCV Monoinfection

Investigators assessed whether increased interleukin-18 could explain the increased incidence and progression of inflammatory conditions seen with HIV/HCV coinfection. [Clin Infect Dis] Abstract

A Combinatorial CRISPR-Cas9 Attack on HIV-1 DNA Extinguishes All Infectious Provirus in Infected T Cell Cultures

The authors demonstrated that combinations of two antiviral gRNAs delay viral escape, and identify two gRNA combinations that durably block virus replication. When viral escape is prevented, repeated Cas9 cleavage leads to saturation of major mutations in the conserved target sequences that encode critical proteins. [Cell Rep] Full Article

Increased Frequency of CD39⁺ CD56^bright Natural Killer Cells in HIV-1 Infection Correlates with Immune Activation and Disease Progression

The authors provide first evidence of increased CD39⁺CD56^bright NK cell frequencies during HIV infection, which might have consequences for NK cell function and HIV pathogenesis. [J Acquir Immune Defic Syndr] Abstract

Quantifying Adaptive and Innate Immune Responses in HIV-Infected Participants Using a Novel High Throughput Assay

HIV infection is characterized by persistent immune dysfunction of both the adaptive and innate immune responses. Scientists evaluated these responses using a novel high throughput assay in healthy controls and HIV-infected individuals prior to and following anti-retroviral treatment. [PLoS One] Full Article

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The Current State of Therapeutic and T Cell-Based Vaccines against Human Papillomaviruses

The authors cover various therapeutic and T cell-based vaccines in development for the treatment of human papillomavirus (HPV)-associated diseases. Furthermore, they review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines. [Virus Res] Abstract

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

ContraVir’s Cyclophilin Inhibitor CRV431 Potently Inhibits Essential Pathway in Hepatitis B

ContraVir Pharmaceuticals, Inc. provided new insights into the mechanism of action of its hepatitis B (HBV)-optimized cyclophilin inhibitor CRV431, showing that it effectively blocks a critical interaction between HBV X protein and host cyclophilin A, with nanomolar potency. [ContraVir Pharmaceuticals, Inc.] Press Release

ExpreS2ion and ABIVAX Announce Development Collaboration on the Ebola Prophylaxis and Treatment Program, ABX544

ExpreS2ion Biotechnologies ApS and ABIVAX S.A. have entered into a service agreement and a term sheet for a commercial license agreement under which ExpreS2ion and ABIVAX collaborate in the development of their proprietary prophylactic and treatment for Ebola virus infection, ABX544. [ABIVAX S.A.] Press Release

Canada’s Government Scientists Get Antimuzzling Clause in Contract

Scientists working for the Canadian government have successfully negotiated a clause in their new contract that guarantees their right to speak to the public and the media about science and their research, without needing approval from their managers. [ScienceInsider] Editorial

In Canada, Case Spurs Concern over Misconduct Secrecy

In early 2013, scientists working in a laboratory led by a prominent cancer researcher at the University of British Columbia (UBC) in Vancouver, Canada, were getting worried. They were unable to reproduce results from several of the researcher’s experiments, and suspected some of the original work was fraudulent. An investigation by UBC ultimately confirmed their fears: In 2014, investigators identified 29 instances of scholarly misconduct, 16 of them “serious,” including falsification and fabrication of data, according to university correspondence obtained by Retraction Watch. [ScienceInsider] Editorial

Is Donald Trump Pushing More Scientists towards Political Activism?

Around the world, individual researchers and representatives of scientific societies are signing letters of protest or advice, offering to counsel Trump’s transition team and ramping up efforts to communicate the value of science to the public. [Nature News] Editorial

NEW 19^th International Conference on Infectious Diseases (ICID), 2017
January 26-27, 2017
Sydney, Australia

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Immunology (University of Toronto)

NEW Postdoctoral Fellow – Vaccine Research (Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.)

NEW Postdoctoral Scientist – Virus-Host Interactions (University of Zurich)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – HIV Immunotherapy (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Pre-Clinical In Vivo Studies and Immunology (German Cancer Research Center)

Postdoctoral Research Fellow – CAR T Cell Therapy for HIV Infection (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Viral Infection Modeling (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Research Scientist – Infection (Rush University Medical Center)

Postdoctoral Fellow – Immunology of Chronic HBV Infection (F. Hoffmann-La Roche)

Faculty Position – Senior Immunologist (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Quantitative Infectious Disease Methods (Fred Hutchinson Cancer Research Center)

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