Immunology of Infectious Disease News Volume 5.17 | May 3 2017

TOP STORY

Host DNA Released by NETosis Promotes Rhinovirus-Induced Type-2 Allergic Asthma Exacerbation

Scientists report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, they showed that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis. [Nat Med] Abstract

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Similarity in Viral and Host Promoters Couples Viral Reactivation with Host Cell Migration

The authors compared viral and human promoter sequences and expression to test whether genetic coupling exists and investigated its phenotypic consequences. They showed that viral–host co-evolution is imprinted within promoter gene sequences before transcript or protein interactions. [Nat Commun] Full Article

NLRX1 Negatively Modulates Type I IFN to Facilitate KSHV Reactivation from Latency

Investigators report that NLRX1, a negative regulator of the type I interferon response, is important for optimal Kaposi’s sarcoma-associated herpesvirus (KSHV) reactivation from latency. Depletion of NLRX1 in either iSLK.219 or BCBL-1 cells significantly suppressed global viral transcription levels compared to the control group. Concomitantly, fewer viral particles were present in either cells or supernatant from NLRX1 depleted cells. [PLoS Pathog] Full Article

IL-33/ST2 Pathway Drives Regulatory T Cell Dependent Suppression of Liver Damage upon Cytomegalovirus Infection

Researchers demonstrated that liver regulatory T (Treg) cells are strongly induced in mice infected with murine cytomegaloviruses (CMV). The depletion of Treg cells resulted in severe hepatitis and liver damage without alterations in the virus load. Moreover, liver Treg cells showed a high expression of ST2, a cellular receptor for tissue alarmin IL-33, which is strongly upregulated in the liver of infected mice. [PLoS Pathog] Full Article

Cytotoxic CD8⁺ T Cells Ablation Enhances the Capacity of Regulatory T Cells to Delay Viral Elimination in Theiler’s Murine Encephalomyelitis

The authors tested whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in Theiler’s murine encephalomyelitis (TME) virus-induced demyelinating disease resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells, anti-CD8-antibodies to deplete cytotoxic T cells or with a combination of Treg-expansion and CD8-depletion prior to infection. [Brain Pathol] Abstract

Paper-Based RNA Detection and Multiplexed Analysis for Ebola Virus Diagnostics

Researchers performed isothermal reverse transcription and Recombinase Polymerase Amplification (RT-RPA) of synthetic Ribonucleic Acid (RNA) of Ebola virus using paper microfluidics devices. They further applied this method in Guinea to detect the presence of Ebola virus in human sample RNA extracts, with minimal facilities. RT-RPA results were available in few minutes and demonstrated a sensitivity of 90.0% compared to the gold-standard RT-PCR on a set of 43 patient samples. [Sci Rep] Full Article

Lineage-Specific SNPs for Genotyping of Mycobacterium tuberculosis Clinical Isolates

The authors identified single nucleotide polymorphisms (SNPs) of six representative M. tuberculosis strains from Taiwan by whole-genome sequencing and compared the results to the sequence of the H37Rv reference strain. One hundred and ten SNPs, each unique to one of the six strains, were used to genotype 150 additional isolates by applying DNA mass spectrometry. Lineage-specific SNPs were identified that could distinguish the major lineages of the clinical isolates. [Sci Rep] Full Article

Anti-Mycobacterium Activity of Microbial Peptides in a Silkworm Infection Model with Mycobacterium smegmatis

An in vivo-mimic silkworm infection model with M. smegmatis was established. When silkworms were raised at 37°C following an injection of M. smegmatis cells into the silkworm hemolymph, they died within 48 hours. These results indicated that the silkworm infection model with M. smegmatis is practically useful for the screening of therapeutically effective anti-M. tuberculosis antibiotics. [J Antibiot (Tokyo)] Abstract

HIV

A Versatile Tool for Live-Cell Imaging and Super-Resolution Nanoscopy Studies of HIV-1 Env Distribution and Mobility

Investigators established efficient incorporation of non-canonical amino acids within HIV-1 Env in mammalian cells. The engineered protein retained plasma membrane localization, glycosylation, virion incorporation, and fusogenic activity, and could be rapidly and specifically labeled with synthetic dyes. [Cell Chem Biol] Abstract | Graphical Abstract

Heroin-HIV-1 (H2) Vaccine: Induction of Dual Immunologic Effects with a Heroin Hapten-Conjugate and an HIV-1 Envelope v2 Peptide with Liposomal Lipid A as an Adjuvant

A synthetic heroin analog and a synthetic 42 amino acid V2 loop peptide from A/E strain of HIV-1 gp120 envelope protein that was previously used in a successful Phase III vaccine trial were constructed as antigens together with liposomes containing monophosphoryl lipid A as an adjuvant, to explore the feasibility of producing a dual use vaccine both for treatment of heroin addiction and prevention of HIV-1 infection among injection drug users. [npj Vaccines] Full Article

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Ménage à Trois in the Human Gut: Interactions between Host, Bacteria and Phages

Bacteriophages in the gut are largely unexplored, despite their potential to regulate bacterial communities and thus human health. In addition to helping us understand gut homeostasis, applying an ecological perspective to the study of bacterial and phage communities in the gut will help us to understand how this microbial system functions. [Nat Rev Microbiol] Abstract

Epigenetic and Transgenerational Mechanisms in Infection-Mediated Neurodevelopmental Disorders

The author discusses the potential epigenetic mechanisms underlying the effects of prenatal infections, thereby highlighting how infection-mediated epigenetic reprogramming may contribute to the transgenerational transmission of pathological traits. [Transl Psychiatry] Full Article

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First Ever Evidence of Treatment-Induced Reduction in HIV Reservoirs

ABIVAX announced that the company’s lead therapeutic candidate ABX464 demonstrated the first reduction in HIV reservoirs ever observed in chronically infected HIV patients as measured by total HIV DNA detected in peripheral blood mononuclear cells. [ABIVAX] Press Release

Soligenix Receives FDA Protocol Clearance of Pivotal Phase III Clinical Trial of SGX942 for the Treatment of Oral Mucositis in Head and Neck Cancer Patients

Soligenix, Inc. announced that it has received US Food and Drug Administration (FDA) clearance to advance a pivotal Phase III clinical trial evaluating SGX942 for the treatment of oral mucositis in head and neck cancer patients being treated with chemoradiation. Soligenix plans to begin this study in the second quarter of 2017. [Soligenix, Inc.] Press Release

Emmes Expands Zika Research

The Emmes Corporation announced a contract spanning just over four years for a Phase II study of a Zika vaccine. The contract, valued at up to $27.6 million, expands the initial Phase I testing that began last year. This is the first-ever Phase II study for a Zika vaccine. [The Emmes Corporation] Press Release

Eiger Announces U.S. IND Filing of Pegylated Interferon Lambda for Hepatitis Delta Virus Infection

Eiger BioPharmaceuticals, Inc. announced that the U.S. IND has been filed for Pegylated Interferon Lambda in the treatment of hepatitis delta virus (HDV) infection. U.S. sites are planned for the ongoing Phase II LIMT HDV study, a monotherapy trial of pegylated interferon lambda 1a as a potential treatment for chronic hepatitis D virus infection. [Eiger BioPharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

bioMONTR Labs’ Laboratory Director Receives Achievement Award

bioMONTR Labs announced that its Laboratory Director, Dr. Susan Fiscus, has been named as the 2017 recipient of the Ed Nowakowski Senior Memorial Clinical Virology Award presented by the Pan American Society for Clinical Virology. This accolade is awarded to individuals who have made a major impact on the epidemiology, treatment or understanding of the pathogenesis of viral diseases. [bioMONTR Labs (PR Newswire Association LLC.)] Press Release

NIH to Limit the Amount of Grant Money a Scientist Can Receive

For the first time, the US National Institutes of Health (NIH) will restrict the amount of funding that an individual scientist can hold at any one time, based on a new point system. The move is part of an ongoing effort to make obtaining grants easier for early and mid-career scientists, who face much tougher odds than their more-experienced colleagues. [Nature News] Editorial

Angering Animal Welfare Activists, Mauritius Invites Primate Research Labs to Set Up Shop

Mauritius has decided to get into the business of nonhuman primate experimentation itself even as such work is becoming increasingly constrained in North America and Europe. Last month the move touched off a heated debate in Mauritius’s National Assembly about whether the government could adequately protect the macaques used in research and whether the new industry might endanger a far bigger lifeline for the island—tourism. [ScienceInsider] Editorial

NEW AACR-NCI-EORTC Molecular Targets & Cancer Therapeutics
October 26-30, 2017
Philadelphia, United States

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NEW Scientist I/II – Analytical Development (KBI Biopharma)

NEW Staff Clinician Position – Laboratory of Clinical Infectious Diseases (National Institute of Allergy and Infectious Diseases (NIAID))

NEW Associate Professorship – Virology (Charite – Universitatsmedizin Berlin)

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

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)

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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