Immunology of Infectious Disease News Volume 5.20 | May 24 2017

TOP STORY

Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability

Researchers describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets. [Cell] Abstract | Graphical Abstract

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Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses

The authors mined the human immune response to natural Ebola virus infection and identified monoclonal antibodies (mAbs) with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the glycoprotein (GP) fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate generated in host cell endosomes. [Cell] Abstract | Graphical Abstract

The MicroRNA miR-31 Inhibits CD8⁺ T Cell Function in Chronic Viral Infection

Scientists found that the microRNA miR-31 was strongly induced by activation of the T cell antigen receptor in a pathway involving calcium and activation of the transcription factor NFAT. During chronic infection with lymphocytic choriomeningitis virus clone 13, miR-31-deficent mice recovered from clinical disease, while wild-type mice continued to show signs of disease. [Nat Immunol] Abstract

Impact of Simultaneous Exposure to Arboviruses on Infection and Transmission by Aedes aegypti Mosquitoes

Investigators exposed A. aegypti mosquitoes to chikungunya, dengue-2 or Zika viruses, both individually and as double and triple infections. Their results showed that these mosquitoes can be infected with and can transmit all combinations of these viruses simultaneously. [Nat Commun] Full Article

Crystal Structure of the Receptor Binding Domain of the Spike Glycoprotein of Human Betacoronavirus HKU1

The authors present the crystal structure of HKU1 C-terminal domain at 1.9 Å resolution. The structure consists of three subdomains: core, insertion and subdomain-1 (SD-1). While the structure of the core and SD-1 subdomains of HKU1 are highly similar to those of other β-coronavirus, the insertion subdomain adopts a novel fold, which is largely invisible in the cryo-EM structure of the HKU1 S trimer. [Nat Commun] Full Article

A Core Extended Naphtalene Diimide G-Quadruplex Ligand Potently Inhibits Herpes Simplex Virus 1 Replication

Scientists investigated the possibility to target the herpes simplex virus 1 (HSV-1) G-quadruplexes (G4s) by a core extended naphtalene diimide (c-exNDI) G4 ligand. Biophysical and biomolecular analysis proved that c-exNDI stabilized the HSV-1 G4s in a concentration dependent manner. In MS competition assays, c-exNDI preferentially recognized HSV-1 G4s over cellular telomeric G4s, the most represented G4s within cells; other less abundant cellular G4s were also recognized. [Sci Rep] Full Article

Metabolic Anticipation in Mycobacterium tuberculosis

Researchers identified a metabolic adaptation that is triggered upon entry into hypoxia-induced quiescence but facilitates subsequent cell cycle re-entry. Catabolic remodeling of the cell surface trehalose mycolates of M. tuberculosis specifically generated metabolic intermediates reserved for re-initiation of peptidoglycan biosynthesis. [Nat Microbiol] Abstract

A Malaria Vaccine Protects Aotus Monkeys against Virulent Plasmodium falciparum Infection

Scientists showed that vaccination with apical membrane antigen 1 (AMA1)–RON2L complex in Freund’s adjuvant protects Aotus monkeys against a virulent P. falciparum infection. Vaccination with AMA1 alone gave only partial protection, delaying infection in one of eight animals. However, the AMA1–RON2L complex vaccine completely protected four of eight monkeys and substantially delayed infection in three of the other four animals. [npj Vaccines] Full Article

HIV

Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy

Investigators describe the development of a novel lentiviral vector with a unique genomic structure designed to prevent transfer of HIV-1 packaging sequences to patient cells, thus reducing the total HIV-1 content to just 4.8% of the wild-type genome. This has been achieved by reconfiguring the vector to mediate reverse-transcription with a single strand transfer, instead of the usual two, and in which HIV-1 packaging sequences are not copied. [Mol Ther] Full Article

The CCR5-Antagonist Maraviroc Reverses HIV-1 Latency In Vitro Alone or in Combination with the PKC-Agonist Bryostatin-1

Researchers studied the effect of Maraviroc (MVC), a CCR5 antagonist that activates NF-κB, on HIV-1 replication from latency. HIV-1-latency models based on CCL19 or IL7 treatment, before HIV-1 infection were used. Latently infected primary resting CD4⁺ or central memory T cells were stimulated with MVC alone or in combination with Bryostatin-1, a PKC agonist known to reverse HIV-1 latency. [Sci Rep] Full Article

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Persistent Bacterial Infections and Persister Cells

Many bacteria can infect and persist inside their hosts for long periods of time. This can be due to immunosuppression of the host, immune evasion by the pathogen and/or ineffective killing by antibiotics. Bacteria can survive antibiotic treatment if they are resistant or tolerant to a drug. Persisters are a subpopulation of transiently antibiotic-tolerant bacterial cells that are often slow-growing or growth-arrested, and are able to resume growth after a lethal stress. [Nat Rev Microbiol] Abstract

Viral Hijacking of Host Caspases: An Emerging Category of Pathogen–Host Interactions

Some viruses have developed the ability to co-opt apoptotic caspase activity to facilitate their own proliferation. In these strategies, viral proteins are cleaved by host caspases to create cleavage products with novel activities which facilitate viral replication. This represents a novel and interesting class of viral–host interactions, and also represents a new group of non-apoptotic roles for caspases. [Cell Death Differ] Abstract

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Viriom to Present Results of Pre-Clinical Pharmacokinetic Studies with Elsulfavirine and VM1500A Long Acting Injectable Formulations

Viriom Inc. announced that the data from pre-clinical studies of Elsulfavirine/VM1500A Long Acting Injectable Formulations will be presented. The studies evaluate new options for the treatment and prevention of HIV/AIDS that would allow for infrequent dosing, thus facilitating patients’ adherence, and likely improving long-term treatment outcomes. [Press release from Viriom Inc. discussing research presented at the 9^th International AIDS Society Conference on HIV Science (IAS 2017), Paris] Press Release

CLJI Worldwide Trial Enrolls First Patient in Clinical Study Evaluating the Performance of VIBLOK as a Barrier for Herpes Simplex Virus Transmission in Men and Women

CLJI Worldwide reports the start of the VIBLOK Safety And perFormancE Trial (SAFE Trial). The CLJI Worldwide SAFE Trial will evaluate the performance of VIBLOK for adults infected with herpes simplex virus-2 (HSV-2), the cause of genital herpes. VIBLOK is an investigational device developed to help reduce skin-to-skin HSV-2 transmission. [CLJI Worldwide] Press Release

Merck Receives CHMP Positive Opinion Recommending Approval of ISENTRESS^® (Raltegravir) 600 mg in the European Union

Merck announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending approval of ISENTRESS^® 600 mg film-coated tablets, in combination with other anti-retroviral medicinal products, for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 40 kg. [Merck] Press Release

Academies Calculate How Much Brexit Will Cost U.K. Researchers

Some academic fields in the United Kingdom will have major funding holes to fill once the country leaves the European Union, according to new research commissioned by four U.K. academies. [ScienceInsider] Editorial

What’s in Trump’s 2018 Budget Request for Science?

President Donald Trump unveiled his full 2018 budget request to Congress. The spending plan, for the fiscal year that begins 1 October, fleshes out the so-called skinny budget that the White House released this past March. That plan called for deep cuts to numerous research agencies. [ScienceInsider] Editorial

NEW International Conference on Sexually Transmitted Diseases, Infections & AIDS
September 21-22, 2017
San Antonio, United States

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NEW Scientist – Immunology, Infectious Diseases (Regeneron)

Physician Scientist – Molecular Basis of Microbial Pathogenesis (Virginia Commonwealth University)

Research Scientist – Microbiology / Molecular Biology (Day Zero Diagnostics)

Lab Aide – Infectious Disease Sciences Program (Fred Hutchinson Cancer Research Center)

Research Technician I – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

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)

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

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