Immunology of Infectious Disease News Volume 5.27 | Jul 12 2017

TOP STORY

Open and Closed Structures Reveal Allostery and Pliability in the HIV-1 Envelope Spike

Scientists present high-resolution cryo-electron microscopy structures of subtype B B41 SOSIP envelope glycoprotein trimers in complex with CD4 and antibody 17b, or with antibody b12, at resolutions of 3.7 Å and 3.6 Å, respectively. [Nature] Abstract | Press Release

(Ranked by impact factor of the journal)

Neurodevelopmental Protein Musashi-1 Interacts with the Zika Genome and Promotes Viral Replication

Investigators report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function. [Science] Abstract

An Ocular Commensal Protects against Corneal Infection by Driving an Interleukin-17 Response from Mucosal γδ T Cells

Researchers used a mouse model of ocular surface disease to reveal that commensals were present in the ocular mucosa and had functional immunological consequences. They isolated one such candidate commensal, Corynebacterium mastitidis, and showed that this organism elicited a commensal-specific interleukin-17 response from γδ T cells in the ocular mucosa that was central to local immunity. [Immunity] Full Article | Graphical Abstract

Endosomal NOX2 Oxidase Exacerbates Virus Pathogenicity and Is a Target for Antiviral Therapy

The authors identified that the primary enzymatic source of reactive oxygen species, NOX2 oxidase, is activated by single stranded RNA and DNA viruses in endocytic compartments resulting in endosomal hydrogen peroxide generation, which suppresses antiviral and humoral signaling networks via modification of a unique, highly conserved cysteine residue on Toll-like receptor-7. [Nat Commun] Full Article | Press release

Idiosyncratic MòJiāNg Virus Attachment Glycoprotein Directs a Host-Cell Entry Pathway Distinct from Genetically Related Henipaviruses

Scientists found that MojV-G displays a six-bladed β-propeller fold bearing limited similarity to known paramyxoviral attachment glycoproteins, in particular at host receptor-binding surfaces. They confirmed the inability of MojV-G to interact with known paramyxoviral receptors in vitro, indicating an independence from well-characterized ephrinB2/B3, sialic acid and CD150-mediated entry pathways. [Nat Commun] Full Article

Culling of APCs by Inflammatory Cell Death Pathways Restricts TIM3 and PD-1 Expression and Promotes the Survival of Primed CD8 T Cells

Researchers evaluated the impact of premature cell death of antigen-presenting cells (APCs) by Caspase-1- and RipK3-signaling pathways on CD8⁺ T-cell priming during infection of mice with Salmonella typhimurium. Their results indicate that Caspase1 and RipK3 synergize to rapidly eliminate infected APCs, which does not influence the initial activation of CD8⁺ T cells. [Cell Death Differ] Abstract

Viral Activation of Heparanase Drives Pathogenesis of Herpes Simplex Virus-1

The authors demonstrated that heparanase (HPSE), a host enzyme, is the molecular trigger for multiple pathologies associated with herpes simplex virus-1 (HSV-1) infection. In human corneal epithelial cells, HSV-1 infection upregulates HPSE in a manner dependent on HSV-1 infected cell protein 34.5. HPSE then relocates to the nucleus to regulate cytokine production, inhibits wound closure, enhances viral spread, and thus generates a toxic local environment. [Cell Rep] Full Article | Graphical Abstract

Dual Non-Contiguous Peptide Occupancy of HLA Class I Evoke Antiviral Human CD8 T Cell Response and Form Neo-Epitopes with Self-Antigens

Scientists showed that single short peptides of 8-mer from Latent Membrane Protein 2 of Epstein Barr Virus can bind HLA-A*11:01 and stimulate CD8⁺ cells. [Sci Rep] Full Article

Constitutive Resistance to Viral Infection in Human CD141⁺ Dendritic Cells

By analyzing the susceptibility of primary human dendritic cells (DC) subsets to viral infections, researchers report that CD141⁺ DCs have an innate resistance to infection by a broad range of enveloped viruses, including HIV and influenza virus. In contrast, CD1c⁺ DCs are susceptible to infection, which enables viral antigen production but impairs their immune functions and survival. [Sci Immunol] Full Article

HIV

The Anti-HIV Candidate Abx464 Dampens Intestinal Inflammation by Triggering Il-22 Production in Activated Macrophages

Scientists tested the protective properties of ABX464, a first-in-class anti-HIV drug candidate currently in phase II clinical trials. ABX464 treatment strongly attenuated dextran sulfate sodium (DSS)-induced colitis in mice and produced a long-term protection against prolonged DSS-exposure after drug cessation. [Sci Rep] Full Article | Press Release

NKG2C⁺ Memory-Like NK Cells Contribute to the Control of HIV Viremia during Primary Infection: Optiprim-ANRS 147

Scientists investigated extensively the NKG2C⁺ NK cells at the time of primary HIV infection and its evolution after three months of early antiretroviral therapy (combination antiretroviral therapy). Multiparametric cytometry combined with bioinformatics was used to determine subsets. NK^bright NKG2C⁺ progenitor, NK^dim NKG2C⁺ effector and NK^dim NKG2C⁺CD57⁺ memory-like populations were identified. [Clin Transl Immunology] Full Article

Subscribe to our sister publications: Human Immunology News & Immune Regulation News.

Caspases Control Antiviral Innate Immunity

The authors focus on the cutting-edge discoveries regarding the multifaceted roles of caspases in antiviral innate immunity. [Cell Mol Immunol] Full Article

Antibody Therapies for the Prevention and Treatment of Viral Infections

Researchers summarize some recent advances in identification and characterization of monoclonal antibodies suitable as drug candidates for clinical evaluation, and review some promising candidates in the development pipeline. [npj Vaccines] Full Article

Visit our reviews page to see a complete list of reviews in the immunology of infectious disease research field.

Merck to Present New Data from Clinical Trials Evaluating ISENTRESS^® HD (Raltegravir) and Investigational HIV Therapies Doravirine and MK-8591 at IAS 2017

Merck announced that new data will be presented including late-breaker abstracts from two Phase III pivotal clinical trials. [Press release from Merck Sharp & Dohme Corp. discussing research to be presented at the 9^th IAS Conference on HIV Science (IAS 2017)] Press Release

Entasis Therapeutics and the Global Antibiotic Research & Development Partnership (GARDP) to Develop a New Treatment for Drug-Resistant Gonorrhea

Zoliflodacin, a novel first-in-class oral antibiotic and one of the only treatments in development to address the rapidly-growing threat of drug-resistant gonorrhea will enter pivotal trials, thanks to a new partnership between the not-for-profit Global Antibiotic Research and Development Partnership and Entasis Therapeutics. [Entasis Therapeutics] Press Release

Untreatable Gonorrhoea on the Rise Worldwide

Gonorrhoea is becoming as incurable as it was in the 1920s, before the first drugs to treat it were discovered. More than 60% of countries surveyed around the world have reported cases that resist last-resort antibiotics, according to an announcement by the World Health Organization. The announcement included information about a new gonorrhoea drug in development. [Nature] Editorial | Publication

White House’s Dwindling Science Office Leaves Major Research Programs in Limbo

US President Donald Trump has pledged to shrink the federal government, and he seems to be starting with science. Nearly six months after taking office, Trump has not chosen a science adviser, and the White House’s Office of Science and Technology Policy has dwindled from around 130 staff members under former president Barack Obama to 35. [Nature News] Editorial

In a Rare Move, FDA Reverses Course on Drug Developed by CEO with Ties to Trump

The Food and Drug Administration has changed its tune on an experimental drug for a deadly rare disease, withdrawing a request that the company developing it run another clinical trial. The unusual move comes after President Trump met with the company’s CEO — and promised to speed up what he called a “slow and burdensome” process for drug approvals. [STAT news] Editorial

NEW HIV Immunity and Eradication, a Herrenhausen Symposium
November 2-3, 2017
Hanover, Germany

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

NEW Infectious Disease Outcomes Epidemiologist/Transfusion Safety Research (University of California San Francisco)

NEW Assistant/Associate Professor – Disease-Specific Immunology/Vaccinology (Brown University)

Postdoctoral Position – Cell Biology and Innate Immunity (Molecular Infection Medicine Sweden)

Postdoctoral Research Assistant – Immunology of Infectious Diseases (University of Oxford)

Postdoctoral Position – Infectious Diseases Pathogenesis (Massachusetts General Hospital & Harvard Medical School)

Research Associate – HIV Immunology (University College London)

Postdoctoral Scientist – HIV-1 and Malaria Vaccine Research (Center for Infectious Disease Research)

Postdoctoral Position – HIV in T Cells (Ludwig-Maximilians-Universität München)

Scientist – Immunology, Infectious Diseases (Regeneron)

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

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

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Immunology of Infectious Disease News? Click here to submit!

Comments or suggestions? Submit your feedback here.