Immunology of Infectious Disease News Volume 5.16 | Apr 26 2017

TOP STORY

Exploiting Induced Pluripotent Stem Cell-Derived Macrophages to Unravel Host Factors Influencing Chlamydia trachomatis Pathogenesis

Investigators describe an approach using macrophages derived from human induced pluripotent stem cells (iPSdMs) to study macrophage–Chlamydia interactions in vitro. They showed that iPSdMs support the full infectious life cycle of C. trachomatis in a manner that mimics the infection of human blood-derived macrophages. [Nat Commun] Full Article | Press Release

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Type I Interferons Induced by Endogenous or Exogenous Viral Infections Promote Metastasis and Relapse of Leishmaniasis

The authors showed that the disease-exacerbatory role of Leishmania RNA virus 1 (LRV1) relies on type I IFN production by macrophages and signaling in vivo. Moreover, infecting mice with the LRV1-cured Leishmania guyanensis (LgyLRV1⁻) strain of parasites followed by type I IFN treatment increased lesion size and parasite burden, quantitatively reproducing the LRV1-bearing (LgyLRV1⁺) infection phenotype. [Proc Natl Acad Sci USA] Abstract

Epstein-Barr Virus Ensures B Cell Survival by Uniquely Modulating Apoptosis at Early and Late Times after Infection

Scientists sought to define the mechanism of survival in the absence of LMP1/NFB early after infection. They used BH3 profiling to query mitochondrial regulation of apoptosis and defined a transition from uninfected B cells to early-infected and immortalized cells. [Elife] Full Article | Abstract

Dendritic Cell Maturation, but Not Type I Interferon Exposure, Restricts Infection by HTLV-1, and Viral Transmission to T-Cells

Using in vitro monocyte-derived IL-4 dendritic cells (DCs), transforming growth factor beta DCs and interferon-alpha (IFN)-α DCs that mimic DCs contacting Human T-Lymphotropic Virus type 1 (HTLV-1)-1 in vivo, researchers showed that despite their increased ability to capture HTLV-1 virions, IFN-α DCs restrict HTLV-1 productive infection. They demonstrated that it is not due to the antiviral activity of type–I interferon produced by IFN-α DCs, but that it is likely to be linked to a distinct trafficking route of HTLV-1 in IL-4 DCs vs. IFN-α DCs. [PLoS Pathog] Full Article

Sustained Inhibition of HBV Replication In Vivo after Systemic Injection of AAVs Encoding Artificial Antiviral Primary MicroRNAs

To advance RNA interference-based hepatitis B virus (HBV) gene silencing, mono- and trimeric artificial primary microRNAs (pri-miRs) derived from pri-miR-31 were placed under control of the liver-specific modified murine transthyretin promoter. The sequences, which target the X sequence of HBV, were incorporated into recombinant hepatotropic self-complementary adeno-associated viruses. Systemic intravenous injection of the vectors into HBV transgenic mice at a dose of 1×10¹¹ per animal effected significant suppression of markers of HBV replication for at least 32 weeks. [Mol Ther Nucleic Acids] Full Article

Zika Virus Infection Reprograms Global Transcription of Host Cells to Allow Sustained Infection

To identify novel antiviral targets and to elucidate the mechanisms by which Zika virus (ZIKV) exploits the host cell machinery to support sustained replication, researchers analyzed the transcriptomic landscape of human microglia, fibroblast, embryonic kidney and monocyte-derived macrophage cell lines before and after ZIKV infection. The four cell types differed in their susceptibility to ZIKV infection, consistent with differences in their expression of viral response genes before infection. [Emerg Microbes Infect] Full Article

HIV

Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation

Scientists used targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. They engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization. [Cell Rep] Full Article | Graphical Abstract

The HIV-1 Viral Synapse Signals Human Foreskin Keratinocytes to Secrete Thymic Stromal Lymphopoietin Facilitating HIV-1 Foreskin Entry

Investigators designed methodologies to identify the signals transduced in foreskin keratinocytes following HIV-1-envelope-dependent viral synapse formation. They found that the viral synapse activates the MyD88-independent TLR-4–nuclear factor signaling pathway in keratinocytes and the subsequent secretion of cytokines including thymic stromal lymphopoietin, a cytokine linking innate and T-helper type 2-adaptive immune responses. [Mucosal Immunol] Abstract

A Non-Canonical Binding Interface in the Crystal Structure of HIV-1 gp120 Core in Complex with CD4

Researchers report a crystal structure of the gp120/CD4 complex without the aid of an antibody from HIV-1 CRF07_BC, a strain circulating in China. In addition to the canonical binding surface, a second interacting interface was identified. A mutagenesis study on critical residues revealed that the stability of this interface is important for the efficiency of Env-mediated membrane fusion. [Sci Rep] Full Article

A Novel Mechanism Linking Memory Stem Cells with Innate Immunity in Protection against HIV-1 Infection

The authors studied T stem cell memory (TSCM) and innate immunity. TSCM cells were identified by phenotypic markers of CD4⁺ T cells and they were further characterized into four subsets. These expressed the common IL-2/IL-15 receptors and another subset of APOBEC3G anti-viral restriction factors, both of which were upregulated. [Sci Rep] Full Article

CD₅₆^bright NK IL-⁷Rα Expression Negatively Associates with HCV Level, and IL-⁷-Induced NK Function Is Impaired during HCV and HIV Infections

The authors measured CD127 expression on CD56^bright, CD56^dimCD16⁺, or CD56^negCD16⁺ NK cell subsets of 25 uninfected donors; 34 chronic hepatitis C virus (HCV)-infected, treatment-naïve; 25 HIV-infected, virally suppressed on antiretroviral therapy (ART); and 42 HCV–HIV-coinfected subjects on ART. CD127 expression on CD56^bright NK cells negatively correlated with HCV plasma levels in HCV monoinfection and HCV–HIV coinfection. [J Leukoc Biol] Abstract

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The Immunopathology of Sepsis and Potential Therapeutic Targets

Pivotal for the clinical development of new sepsis therapies is the selection of patients on the basis of biomarkers and/or functional defects that provide specific insights into the expression or activity of the therapeutic target. [Nat Rev Immunol] Abstract

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AmpliPhi Biosciences Announces Presentation of Personalized Bacteriophage Therapy Case Study for Life-Threatening Antibiotic-Resistant Infection

AmpliPhi Biosciences Corporation announced that a case study highlighting the successful treatment of a critically ill patient with a multidrug-resistant Acinetobacter baumannii infection will be featured in an oral presentation. [Press release from AmpliPhi Biosciences Corporation discussing research to be presented at the Centennial Celebration of Bacteriophage Research, Paris] Press Release

Pivotal Phase III Study Underscores Efficacy Of Zavicefta^™ (Ceftazidime-Avibactam) for Treatment of Hospital-Acquired Pneumonia

Positive results of the REPROVE1 Study showed that patients diagnosed with hospital-acquired pneumonia, treated with Zavicefta, a novel combination antibiotic for the treatment of certain known or suspected Gram-negative bacterial infections, or Meropenem, a broad spectrum carbapenem antibiotic currently considered the standard of care, experienced comparable rates of clinical cure at test-of-cure 21-25 days after randomization. [Press release from Pfizer Inc. discussing research presented at the 27^th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna] Press Release

Theravance Biopharma Reports Positive Clinical Response Rates for Patients in TOUR^™ Observational Patient Registry

Theravance Biopharma, Inc. announced that new preliminary data from the ongoing Telavancin Observational Use Registry (TOUR^™) study are the focus of three poster presentations. The presented findings report positive clinical responses for VIBATIV treatment ranging from 58.3% to 75.3% in these infection types. Positive clinical response was defined as cure or improvement leading to step-down oral therapy. [Press release from Theravance Biopharma, Inc. discussing research presented at the 27^th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna] Press Release

Arsanis Announces Initial Clinical Data for ASN100

Arsanis, Inc. announced the presentation of data to highlight the Phase I safety and pharmacokinetics of ASN100, the company’s lead clinical candidate currently being evaluated in a Phase II trial for the prevention of Staphylococcus aureus pneumonia in high-risk, mechanically ventilated patients as well as new research findings for ASN100 and two pre-clinical mAb programs, ASN200 and ASN300, which target infections caused by multi-drug resistant strains of the Gram-negative pathogens Escherichia coli and Klebsiella pneumoniae. [Press release from Arsanis, Inc. discussing research presented at the 27^th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Vienna] Press Release

Merck Announces New Phase II Data on Investigational Triple Combination Therapy MK-3682B for Chronic Hepatitis C

Merck announced the first sustained virologic response results 12 weeks after completion of therapy from C-SURGE, an ongoing, open label Phase II clinical trial evaluating MK-3682B, the company’s investigational triple-combination therapy in treatment-experienced patients with hepatitis C virus genotype 1 infection for whom treatment with approved direct-acting antiviral regimens had failed. The study showed that 100 percent of patients who completed 16 weeks of treatment plus ribavirin achieved SVR12 and 100 percent of patients who completed 24 weeks of treatment achieved SVR12. [Press release from Merck discussing research presented at the International Liver Congress^™ 2017, Amsterdam] Press Release

Eight Weeks of Treatment with AbbVie’s Investigational, Pan-Genotypic Regimen of Glecaprevir/Pibrentasvir (G/P) Achieved High SVR₁₂ Rates in Challenging to Treat Genotype 3 Chronic Hepatitis C

AbbVie announced high SVR₁₂ rates were achieved with eight weeks of treatment with its investigational, once-daily, ribavirin-free, pan-genotypic regimen of glecaprevir/pibrentasvir (G/P) in patients with challenging to treat genotype 3 (GT3) chronic hepatitis C virus (HCV) infection. In results from the Phase III ENDURANCE-3 study, 95 percent of GT3 chronic HCV infected patients without cirrhosis and who are new to treatment achieved sustained virologic response at 12 weeks post-treatment following eight weeks of treatment with G/P. [Press release from AbbVie Inc. discussing research presented at the International Liver Congress^™ 2017, Amsterdam] Press Release

GenMark Achieves CE Mark for Its ePlex^® Blood Culture Identification Fungal Pathogen Panel

GenMark Diagnostics, Inc. announced it has achieved CE Mark under the European In Vitro Diagnostic Devices Directive for its ePlex Blood Culture Identification Fungal Pathogen (BCID-FP) Panel. BCID-FP is the first panel in the GenMark Sepsis Solution, which will also include BCID Gram-Positive and Gram-Negative panels. [GenMark Diagnostics, Inc.] Press Release

John Aitchison, Leader in Systems Biology, Named New President of the Center for Infectious Disease Research

In a unanimous vote, the Board of Trustees of the Center for Infectious Disease Research appointed Dr. John Aitchison as the third president and director in their 40 year history. [Center for Infectious Disease Research] Press Release

California’s $3-Billion Bet on Stem Cells Faces Final Test

When California voters approved US$3 billion in funding for stem-cell research in 2004, biologists flocked to the state, and citizens dreamed of cures for Parkinson’s disease and spinal-cord injuries. Now, the pot of money — one of the biggest state investments in science — is running dry before treatments have emerged, raising questions about whether Californians will pour billions more into stem-cell research. [Nature News] Editorial

NSF’s Uphill Road to Making Prestigious Early Career Award More Diverse

Only five women have won the National Science Foundation’s (NSF) annual Alan T. Waterman Award in its 41-year history, and no woman of color has ever been selected. The 2017 winners announced this month mark the 13^th year in a row that the $1 million research prize has gone to a man (two, actually, including the second black scientist ever chosen.) [ScienceInsider] Editorial

The Broad Institute Is Testing the Limits of What ‘Nonprofit’ Means

When a federal patent court ruled that the nonprofit Broad Institute of MIT and Harvard could legally license its version of the CRISPR-Cas9 genome-editing system, it opened the door to millions of dollars of revenue for the institute. It also contributed to the seismic shift occurring in science whereby tax-exempt research institutes established under an emerging model of “free market philanthropy” can amass money to further their research and protect their commercial interests. [STAT News] Editorial

What Happened at March for Science Events around the World

Tens of thousands of people gathered in Washington DC, and at least 600 other cities around the world, in what may have been one of the largest-ever demonstrations in support of scientific research and evidence-based policymaking. [Nature News] Editorial

French Scientists Focus on the Big Political Picture

Researchers in France overwhelmingly oppose the far right and can stamp out its rise by turning out to register their disapproval. [Nature News] Editorial

NEW 3^rd CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference
September 6-9, 2017
Mainz/Frankfurt, Germany

NEW Society for Leucocyte Biology (SLB)
October 5-7, 2017
Vancouver, Canada

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

NEW Clinical Assistant II – Seattle Vaccine Trials Unit (Fred Hutchinson Cancer Research Center)

NEW Assistant or Associate Member – Microbiome (Fred Hutchinson Cancer Research Center)

Assistant Professor – Infectious Disease Epidemiology (The University of Warwick)

Junior Research Group Leader – Infection Biology (Julius-Maximilians Universitat Wurzburg)

Faculty and Postdoctoral Positions – Molecular Pathogenesis (Nankai University)

Postdoctoral Positions – Functional Genomics of Virus-Host Interactions (University of Strasbourg)

Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Lecturer – Infectious Diseases (Virology)

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

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