Immunology of Infectious Disease News Volume 5.32 | Aug 16 2017

TOP STORY

Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-Classical MHC Class II Gene H2-Ob

The authors report positional cloning of the gene responsible for production of retrovirus-neutralizing antibodies in mice of the I/LnJ strain. It encodes the beta subunit of the non-classical major histocompatibility complex class II (MHC-II)-like molecule H2-O, a negative regulator of antigen presentation. The recessive and functionally null I/LnJ H2-Ob allele supported the production of virus-neutralizing antibodies independently of the classical MHC haplotype. [Immunity] Abstract | Press Release | Graphical Abstract

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Nasopharyngeal Infection by Streptococcus pyogenes Requires Superantigen-Responsive Vβ-Specific T Cells

Researchers demonstrated that passive immunization against the Vβ8-targeting superantigens (SAgs) streptococcal pyrogenic exotoxin A (SpeA), or active immunization with either wild-type or a nonfunctional SpeA mutant, protected mice from nasopharyngeal infection; however, only passive immunization, or vaccination with inactive SpeA, resulted in high-titer SpeA-specific antibodies in vivo. Mice vaccinated with wild-type SpeA rendered Vβ8⁺ T cells poorly responsive, which prevented infection. [Proc Natl Acad Sci USA] Abstract

Inhibitors of the Histone Methyltransferases EZH2/1 Induce a Potent Antiviral State and Suppress Infection by Diverse Viral Pathogens

The histone H3K27 methyltransferases EZH2 and EZH1 (EZH2/1) are epigenetic repressors that suppress gene transcription via propagation of repressive H3K27me3-enriched chromatin domains. However, while EZH2/1 are implicated in the repression of herpesviral gene expression, inhibitors of these enzymes suppressed primary herpes simplex virus (HSV) infection in vitro and in vivo. These compounds blocked lytic viral replication following induction of HSV reactivation in latently infected sensory ganglia. [mBio] Full Article | Press Release

Differential Epitope Recognition in the Immunodominant Staphylococcal Antigen a of Staphylococcus aureus by Mouse Versus Human IgG Antibodies

Patients with the genetic blistering disease epidermolysis bullosa displayed high immunodominant staphylococcal antigen A (IsaA)-specific IgG levels that could potentially be protective against S. aureus. Mice actively immunized with IsaA were not protected against S. aureus infection. Researchers aimed to explain these differences in IsaA-specific immune responses. [Sci Rep] Full Article

Characterization of Mycobacterium tuberculosis–Specific Cells Using MHC Class II Tetramers Reveals Phenotypic Differences Related to HIV Infection and Tuberculosis Disease

A total of 86 participants from a tuberculosis (TB)-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M. tuberculosis–specific MHC class II tetramers. Investigators examined the phenotype as well as function of ex vivo M. tuberculosis–specific tetramer⁺CD4⁺ T cells using flow cytometry. The numbers of M. tuberculosis–specific tetramer⁺CD4⁺ T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. [J Immunol] Abstract

Vomocytosis of Live Pathogens from Macrophages Is Regulated by the Atypical MAP Kinase ERK5

The authors used a targeted inhibitor screen to identify the MAP kinase ERK5 as a critical suppressor of vomocytosis. Pharmacological inhibition or genetic manipulation of ERK5 activity significantly raised vomocytosis rates in human macrophages, whereas stimulation of the ERK5 signaling pathway inhibited vomocytosis. [Sci Adv] Full Article | Press Release

HIV

Partial Efficacy of a Broadly Neutralizing Antibody against Cell-Associated SHIV Infection

To evaluate whether broadly neutralizing antibodies can prevent infection after cell-associated viral challenge, scientists infused pigtail macaques with PGT121 or an isotype control and challenged animals one hour later intravenously with simian/human immunodeficiency virus (SHIV)_SF162P3^–infected splenocytes. [Sci Transl Med] Abstract

HIV-1 Nef-Induced Cardiotoxicity through Dysregulation of Autophagy

The authors investigated the effect of the HIV-1 auxiliary protein, Nef, which is suspected of extracellular release by infected CD4⁺ T cells on protein quality control and autophagy in cardiomyocytes. [Sci Rep] Full Article

Interferon-Inducible CD169/Siglec1 Attenuates Anti-HIV-1 Effects of IFN-α

Researchers hypothesized that type I interferon (IFN)-inducible CD169 could facilitate productive HIV-1 infection in myeloid cells in cis and CD4⁺ T cells in trans and thus offset antiviral effects of type I IFN. [J Virol] Abstract

Interaction between Herpesvirus Entry Mediator and HSV-2 Glycoproteins Mediates HIV-1 Entry of HSV-2-Infected Epithelial Cells

Herpesvirus entry mediator (HVEM), a herpes simplex virus type 2 (HSV-2) entry receptor, is highly expressed on human immunodeficiency virus type 1 (HIV-1) target cells (CD4⁺ T cells) and may be incorporated into HIV-1 virions, while HSV-2 glycoproteins can be present on the infected cell surface. Since HVEM–gD interaction together with gB/gH/gL is essential for HSV-2 entry, HVEM-bearing HIV-1 may enter HSV-2-infected cells through such interactions. Scientists confirmed the presence of HVEM on HIV-1 virions and glycoproteins on the HSV-2-infected cell surface. [J Gen Virol] Abstract

Gut-Homing Δ42PD1⁺Vδ2 T Cells Promote Innate Mucosal Damage via TLR4 during Acute HIV Type 1 Infection

Investigators report a Vδ2 subset of gut-homing γδ T cells with significantly upregulated Δ42PD1 in acute HIV-1 patients compared to chronic HIV-1 patients and healthy controls. The frequency of Δ42PD1⁺Vδ2 cells correlated positively with plasma levels of pro-inflammatory cytokines and fatty-acid-binding protein before detectable lipopolysaccharide in acute patients. [Nat Microbiol] Abstract

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Humanized Mouse Models of Latent HIV Infection

The authors summarize recent studies using humanized mouse models to examine different aspects of the viral reservoir. [Curr Opin Virol] Abstract

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Einstein Researchers Awarded Three NIH Grants Totaling $12 Million to Fight Virulent Viruses

The NIH has awarded Einstein researchers three grants totaling more than $12 million to protect against three deadly viruses—Ebola, Marburg and hantavirus. [Albert Einstein College of Medicine] Press Release

Aradigm Awarded NIH Grant to Investigate the Treatment of Pulmonary Non-Tuberculous Mycobacterial (PNTM) Infections with Linhaliq

The National Institute of Allergy and Infectious Diseases and National Institutes of Health (NIH) awarded Aradigm Corporation a Small Business Initiative Research grant to investigate the treatment of two pulmonary non-tuberculous mycobacteria infections, Mycobacterium avium and Mycobacterium abscessus, with Aradigm’s inhaled liposomal ciprofloxacin products Linhaliq^™ and Lipoquin^®. [Aradigm Corporation] Press Release

Gilead Announces U.S. FDA Priority Review Designation for Fixed-Dose Combination of Bictegravir, Emtricitabine and Tenofovir Alafenamide for Treatment of HIV

Gilead Sciences, Inc. announced that the U.S. FDA has granted priority review for the company’s New Drug Application for an investigational, fixed-dose combination of bictegravir, a novel investigational integrase strand transfer inhibitor, and emtricitabine/tenofovir alafenamide, a dual-NRTI backbone, for the treatment of HIV-1 infection. [Gilead Sciences, Inc.] Press Release

Trump Offers His First List of Science Priorities, and It’s America First

President Donald Trump has translated his campaign promise to “make America great again” into his administration’s first blueprint for federal investment in science and technology. [ScienceInsider] Editorial

China’s Embrace of Embryo Selection Raises Thorny Questions

Fertility centers are making a massive push to increase preimplantation genetic diagnosis in a bid to eradicate certain diseases. [Nature News] Editorial

Budget Cuts Fuel Frustration among Japan’s Academics

Japan’s premier scientific research institution, RIKEN, turned 100 this year, and celebrated with a grand ceremony attended by the empress and emperor. But not everybody was in the mood to party. In the old days, RIKEN was known as a paradise for scientists because of its generous funding. No longer: as Japan cuts off funds in the face of continuing financial uncertainty, the cracks are starting to show. [Nature News] Editorial

NEW American Society for Cell Biology (ASCB) – European Molecular Biology Organization (EMBO) 2017 Meeting
December 2-6, 2017
Philadelphia, Pennsylvania, United States

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NEW Assistant or Associate Professor – Virology (University of Iowa)

Faculty Positions – Host-Pathogen Interactions (University of Chicago at Illinois)

Junior Professorship – Systems Biology of Human Parasites (Universität Hamburg)

Senior Bioinformatician – Malaria Genomics (Wellcome Trust Sanger Institute)

Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte. Ltd.)

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

Full Faculty Member – Immunology (Fred Hutchinson Cancer Research Center)

Research Fellow – HIV/AIDS Research (Dana-Farber Cancer Institute)

Infectious Disease Outcomes Epidemiologist – Transfusion Safety Research (University of California, San Francisco)

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

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)

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