Immunology of Infectious Disease News Volume 5.03 | Jan 25 2017

TOP STORY

Coexistence of Potent HIV-1 Broadly Neutralizing Antibodies and Antibody-Sensitive Viruses in a Viremic Controller

The authors describe an HIV-1 controller expressing HLA-B57*01 and HLA-B27*05 who maintained low viral loads for 30 years after infection and developed broad and potent serologic activity against HIV-1. [Sci Transl Med] Abstract

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A Broadly Protective Therapeutic Antibody against Influenza B Virus with Two Mechanisms of Action

Scientists used an in vivo plasmablast enrichment technique to isolate a human monoclonal antibody, 46B8 that neutralizes all Influenza B viruses (IBVs) tested in vitro and protects mice against lethal challenge of all IBVs tested when administered 72 hours post infection. [Nat Commun] Full Article

Critical Role of CXCL4 in the Lung Pathogenesis of Influenza (H1N1) Respiratory Infection

Researchers showed that chemokine (C-X-C motif) ligand 4 (CXCL4) is associated with pulmonary influenza infection and has a critical role in protecting mice from fatal H1N1 virus respiratory infection. CXCL4 knockout resulted in diminished viral clearance from the lung and decreased lung inflammation during early infection but more severe lung pathology relative to wild-type mice during late infection. [Mucosal Immunol] Abstract

Early Secreted Antigenic Target of 6-kDa of Mycobacterium tuberculosis Stimulates IL-6 Production by Macrophages through Activation of STAT3

As early secreted antigenic target of 6 kDa (ESAT-6) of M. tuberculosis is an essential virulence factor and macrophages are critical for tuberculosis infection and immunity, researchers studied ESAT-6 stimulated IL-6 production by macrophages. [Sci Rep] Full Article

Neutrophils Are Dispensable in the Modulation of T Cell Immunity against Cutaneous HSV-1 Infection

Using a mouse model of cutaneous herpes simplex virus type 1 (HSV-1) infection investigators explored potential contributions of neutrophils toward anti-viral immunity. [Sci Rep] Full Article

Defective T-Cell Control of Epstein–Barr Virus Infection in Multiple Sclerosis

Scientists undertook a comprehensive analysis of the T-cell response to Epstein–Barr virus (EBV) in multiple sclerosis, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus, in 95 patients and 56 EBV-seropositive healthy subjects. [Clin Transl Immunology] Full Article

HIV

Follicular CD8 T Cells Accumulate in HIV Infection and Can Kill Infected Cells In Vitro via Bispecific Antibodies

Scientists demonstrated that HIV infection induces marked changes in the phenotype, frequency, and localization of CD8 T cells within the lymph node (LN). Significantly increased frequencies of CD8 T cells in the B cell follicles and germinal centers were found in LNs from treated and untreated HIV-infected individuals. [Sci Transl Med] Abstract

HIV-1 Activates T Cell Signaling Independently of Antigen to Drive Viral Spread

HIV-1 spreads between CD4 T cells most efficiently through virus-induced cell-cell contacts. To test whether this process potentiates viral spread by activating signaling pathways, investigators developed an approach to analyze the phosphoproteome in infected and uninfected mixed-population T cells using differential metabolic labeling and mass spectrometry. [Cell Rep] Full Article | Graphical Abstract

Dynamic Modulation of Expression of Lentiviral Restriction Factors in Primary CD4⁺ T Cells following SIV Infection

Expression of 45 confirmed and putative HIV/SIV restriction factors was analyzed in CD4⁺ T cells from peripheral blood and jejunum in rhesus macaques, revealing distinct expression patterns in naïve and memory subsets. [J Virol] Abstract

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Immunobiology of Ebola and Lassa Virus Infections

The contribution of specific immune responses to disease differs between Ebola virus and Lassa virus. The authors examine innate and adaptive immune responses to these viruses with the goal of delineating responses that are associated with protective versus pathogenic outcomes. [Nat Rev Immunol] Abstract

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Enanta Announces EMA Grants Accelerated Assessment, Validates Marketing Authorization Application for AbbVie’s Investigational HCV Regimen of Glecaprevir/Pibrentasvir (G/P) for the Treatment of All Major Genotypes (GT1-6) of Chronic Hepatitis C

Enanta Pharmaceuticals, Inc. announced that AbbVie’s marketing authorization application for its investigational, pan-genotypic regimen of G/P for the treatment of all major chronic hepatitis C virus (HCV) genotypes, has been validated by the European Medicines Agency (EMA) and is now under accelerated assessment. [Enanta Pharmaceuticals, Inc.] Press Release

Arsanis Announces First Patient Dosed in Global Phase II Study of ASN100 for Prevention of Staphylococcus aureus Pneumonia

Arsanis, Inc. announced that the first patient was dosed in a Phase II clinical study of its lead program, ASN100. The primary objective of this study is to evaluate the safety, tolerability, and efficacy of a single dose of ASN100 versus placebo for the prevention of S. aureus pneumonia in high-risk, mechanically ventilated patients. [Arsanis, Inc.] Press Release

Candidates from Ethiopia, United Kingdom, and Pakistan Will Compete for WHO’s Top Slot

The World Health Organization (WHO) announced who will be up for election to the post of director-general in May. They are: former Ethiopian health minister and minister of foreign affairs Tedros Adhanom Ghebreyesus; British physician and United Nations official David Nabarro; and Pakistani cardiologist and former science minister Sania Nishtar. [Science Insider] Editorial

Memo Freezing NIH Communications with Congress Triggers Jitters

Is the National Institutes of Health (NIH) part of the clampdown by the Trump administration on communications at science agencies? That’s how some are reacting to White House directive telling NIH to halt correspondence with public officials and hold off on new policies. But some observers say the NIH directive is not unusual for a new administration. [ScienceInsider] Editorial

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Postdoctoral Research Fellow – HIV Immunotherapy (Fred Hutchinson 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)

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