Immunology of Infectious Disease News Volume 5.18 | May 10 2017

TOP STORY

The RNA Exosome Syncs IAV-RNAPII Transcription to Promote Viral Ribogenesis and Infectivity

Researchers showed that influenza A virus (IAV) ribogenesis and growth are suppressed by impaired RNA exosome activity. Mechanistically, the nuclear RNA exosome coordinates the initial steps of viral transcription with RNAPII at host promoters. The viral polymerase complex co-opts the nuclear RNA exosome complex and cellular RNAs en route to 3′ end degradation. [Cell] Abstract | Graphical Abstract

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RhoD Inhibits RhoC-ROCK-Dependent Cell Contraction via PAK6

Scientists demonstrated that the vaccinia virus protein F11, which localizes to the plasma membrane, is required for ROCK-mediated cell contraction from two hours post infection. F11-induced cell contraction is dependent on RhoC and not RhoA signaling to ROCK. Moreover, RhoC-driven cell contraction depends on the upstream inhibition of RhoD signaling by F11. [Dev Cell] Full Article | Graphical Abstract

Nontargeted Metabolomics Reveals the Multilevel Response to Antibiotic Perturbations

Investigators showed that rapid metabolic changes can reflect drug mechanisms of action and reveal the active role of metabolism in mediating the first stress response to antimicrobials. They uncovered a role for ammonium imbalance in aggravating chloramphenicol toxicity and the essential function of deoxythymidine 5′-diphosphate-rhamnose synthesis for the immediate transcriptional upregulation of GyrA in response to quinolone antibiotics. [Cell Rep] Full Article | Graphical Abstract

Identification of Tp0751 (Pallilysin) as a Treponema pallidum Vascular Adhesin by Heterologous Expression in the Lyme Disease Spirochete

The study of T. pallidum vascular adhesins is hindered by the uncultivable nature of this pathogen. The authors overcame these limitations by expressing T. pallidum adhesin Tp0751 (pallilysin) in an adhesion-attenuated strain of the cultivable spirochete Borrelia burgdorferi. [Sci Rep] Full Article

Characterization of Retroviral Infectivity and Superinfection Resistance during Retrovirus-Mediated Transduction of Mammalian Cells

Scientists engineered two murine stem cell virus-based retroviral vectors expressing dual fluorescence proteins and antibiotic markers, and analyzed virion production efficiency and virion stability, dynamic infectivity and superinfection resistance in different cell types, and strategies to improve transduction efficiency. They found that the highest virion production occurred between 60 and 72 hours after transfection. [Gene Ther] Full Article

The Role of PD-1 in Regulation of Macrophage Apoptosis and Its Subversion by Leishmania donovani

The authors studied whether the programmed death-1 receptor (PD-1) pathway has any role in eliciting macrophage apoptosis and, if so, then how the intra-macrophage parasite, L. donovani modulates PD-1 pathway for protecting its niche. Resting macrophages when treated with H₂O₂ showed increased PD-1 expression and apoptosis, which was further enhanced on PD-1 agonist treatment. [Clin Transl Immunology] Full Article

HIV

HIV Reprograms Human Airway Basal Stem/Progenitor Cells to Acquire a Tissue-Destructive Phenotype

Given that emphysema originates around the airways and that human airway basal cells (BCs) are adult airway stem/progenitor cells, researchers hypothesized that HIV reprograms BCs to a distinct phenotype that contributes to the development of emphysema. Their data indicated that HIV binds to but does not replicate in BCs. [Cell Rep] Full Article | Graphical Abstract

Structural Basis for Importin-α Binding of the Human Immunodeficiency Virus Tat

Investigators established that the HIV-1 trans-activator of transcription (Tat):nuclear localization signal/cell penetrating peptide is able to form a stable and direct interaction with the classical nuclear import receptor importin-α and using x-ray crystallography, they have determined the molecular interface and binding determinants to a resolution of 2.0 Å. [Sci Rep] Full Article

A Common Anti-CMV Drug, Ganciclovir, Inhibits HIV-1 Replication in Human Tissues Ex Vivo

Investigators showed that ganciclovir, the active form of valganciclovir, has a direct suppressive activity on HIV replication in human tissues ex vivo, including HIV-1 of laboratory strains, drug-resistant and primate isolates. They deciphered the mechanism of this inhibition and showed that GCV-TP is incorporated in the nascent DNA chain and acts as a delayed chain terminator. [AIDS] Abstract

Emergence of CXCR4-Tropic HIV-1 Variants followed by Rapid Disease Progression in Hemophiliac Slow Progressors

The association between emergence of CXCR4-tropic HIV-1 variants (X4 variants) and disease progression of HIV-1 infection has been reported. However, it is not known whether the emergence of X4 variants is the cause or result of HIV-1 disease progression. [PLoS One] Full Article

Trans-Dissemination of Exosomes from HIV-1-Infected Cells Fosters Both HIV-1 Trans-Infection in Resting CD4⁺ T Lymphocytes and Reactivation of the HIV-1 Reservoir

Researchers report that trans-dissemination of exosomes from HIV-1-infected cells induces cell activation in resting CD4⁺ T lymphocytes, which appears stronger with mature than immature dendritic cells (DCs). Using purified preparations of both HIV-1 and exosomes, they observed that mDC-mediated trans-dissemination of exosomes from HIV-1-infected cells to resting CD4⁺ T lymphocytes induced efficient trans-infection and HIV-1 expression in target cells. [Arch Virol] Abstract

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Broad-Spectrum Agents for Flaviviral Infections: Dengue, Zika and Beyond

Researchers summarize and comment on the opportunities for broad-spectrum agents that are active against multiple flaviviruses. Broad-spectrum activity is particularly desirable to prepare for the next flaviviral epidemic, which could emerge from as-yet unknown or neglected viruses. [Nat Rev Drug Discov] Full Article

Current Application of CRISPR/Cas9 Gene-Editing Technique to Eradication of HIV/AIDS

The authors summarize the most recent progress in the application of the clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) gene-editing technique to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) therapy and elimination. Future directions and trends of such applications are also discussed. [Gene Ther] Abstract

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IBM Scientists Use Big Data to Develop New Strategies to Help Address Ebola

IBM announced its researchers have used big data analytics to assess the impact of infected animal carriers, or an animal reservoir, in the spread of the Ebola virus in a way not been previously done for earlier disease models. Direct contact with the infected animal – most likely a bat or large snake — whether by touching or eating it — can cause the disease to enter the human population, and then spread. [IBM] Press Release

PaxVax Initiates Clinical Trials of a Modernized Adenovirus Vaccine in Collaboration with the U.S. Army Medical Materiel Development Activity and the Walter Reed Army Institute of Research to Protect U.S. Military Personnel

PaxVax announced the initiation of a new clinical trial program – the first initiative to modernize the Adenovirus Serotypes 4 and 7 vaccine in more than 30 years. PaxVax is developing an updated and improved version of the vaccine. The vaccine, known as the Modernized Production Adenovirus Vaccine Prototype A, will ultimately be administered to U.S. service members during basic training. [PaxVax] Press Release

Soligenix Receives Japanese Patent for ThermoVax^® Vaccine Heat Stabilization Platform Technology

Soligenix, Inc. announced that it has been granted a Japanese patent further extending protection around ThermoVax^® including coverage of the company’s ricin toxin vaccine candidate, RiVax^®. ThermoVax^® is a proprietary vaccine heat stabilization platform technology and the patent, entitled “Thermostable vaccine compositions and methods of preparing same.” [Soligenix, Inc.] Press Release

Meissa Announces Award of NIH SBIR Grant to Support Development of Multivalent Human Rhinovirus Vaccine Candidate

Meissa Vaccines announced that it has been awarded a Phase I SBIR grant by the National Institutes of Health entitled “Development of polyvalent inactivated rhinovirus vaccine”. The grant will allow Meissa to advance its second product candidate towards an IND, by funding the generation of multiple rhinovirus serotypes and the development of innovative analytical tests to identify and quantify each serotype in the multivalent vaccine. [Meissa Vaccines (PR Newswire Association LLC.)] Press Release

The Secret War against Counterfeit Science

China is famous for knock-off DVDs, Louis Vuitton bags and Rolex watches. But counterfeit reagents aren’t on sale in busy public markets. They are sold through sophisticated websites, mixed in with legitimate supplies, and sourced and sold using a network of unwitting partners. [Nature News] Editorial

Science Publishers Try New Tack to Combat Unauthorized Paper Sharing

The unauthorized sharing of copyrighted research papers is on the rise, say analysts who track the publishing industry. Faced with this problem, science publishers seem to be changing tack in their approach to researchers who breach copyright. [Nature News] Editorial

Biotech Execs, Academic Leaders Make Case for NIH Funding at White House Meeting

Could the Trump administration be changing its mind about slashing funding for the National Institutes of Health (NIH)? Scientific leaders were optimistic after meeting at the White House with several biotech executives to discuss the “ecosystem” in which federally funded basic research leads to discoveries that companies turn into treatments. [ScienceInsider] Editorial

NEW American College of Allergy, Asthma, & Immunology (ACAAI)
October 26-30, 2017
Boston, United States

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NEW Cell Biology Scientists – T Cells Responsive to Various Infectious Disease Targets (Immunocore)

Scientist I/II – Analytical Development (KBI Biopharma)

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

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

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