Immunology of Infectious Disease News Volume 2.46 | Nov 26 2014

Metformin as Adjunct Antituberculosis Therapy
The antidiabetic drug metformin controls the growth of drug-resistant Mycobacterium tuberculosis strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. [Sci Transl Med] Abstract

Exosomes Secreted by Nematode Parasites Transfer Small RNAs to Mammalian Cells and Modulate Innate Immunity
Scientists demonstrate that the gastrointestinal nematode Heligmosomoides polygyrus, which infects mice, secretes vesicles containing microRNAs and Y RNAs as well as a nematode Argonaute protein. Administration of the nematode exosomes to mice suppresses Type 2 innate responses and eosinophilia induced by the allergen Alternaria. [Nat Commun] Full Article | Press Release

Basophil-Mediated Protection against Gastrointestinal Helminths Requires IgE-Induced Cytokine Secretion
Using mixed bone marrow chimeras, scientists found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. [Proc Natl Acad Sci USA] Abstract

Actin Polymerization as a Key Innate Immune Effector Mechanism to Control Salmonella Infection
The mechanism governing how inflammasomes mediate intracellular bacterial-killing and clearance in host macrophages remains unknown. Investigators show that actin polymerization is required for NLRC4-dependent regulation of intracellular bacterial burden, inflammasome assembly, pyroptosis, and IL-1β production. [Proc Natl Acad Sci USA] Abstract | Press Release

Human Cytomegalovirus Vaccine Based on the Envelope gH/gL Pentamer Complex
The authors describe an innovative vaccine strategy to induce serum neutralizing antibodies of impressive magnitude against human Cytomegalovirus in two animal models. [PLoS Pathog] Full Article | Press Release

Shed GP of Ebola Virus Triggers Immune Activation and Increased Vascular Permeability
Researchers show that shed glycoprotein GP released from virus-infected cells binds and activates non-infected dendritic cells and macrophages causing the massive release of pro- and anti-inflammatory cytokines and also affects vascular permeability. [PLoS Pathog] Full Article | Editorial

HIV

Macrophage Infection via Selective Capture of HIV-1-Infected CD4⁺ T Cells
Researchers find that macrophages selectively capture and engulf HIV-1-infected CD4⁺ T cells leading to efficient macrophage infection. Infected T cells, both healthy and dead or dying, were taken up through viral envelope glycoprotein-receptor-independent interactions, implying a mechanism distinct from conventional virological synapse formation. [Cell Host Microbe] Abstract | Graphical Abstract

Natural Polymorphisms in Human APOBEC3H and HIV-1 Vif Combine in Primary T Lymphocytes to Affect Viral G-to-A Mutation Levels and Infectivity
Scientists demonstrate that stable/unstable phenotypes are an intrinsic property of endogenous APOBEC3H proteins in primary CD4⁺ T lymphocytes and confer differential resistance to HIV-1 infection in a manner that depends on natural variation in the Vif protein of the infecting virus. [PLoS Genet] Full Article | Press Release

HIV-1 Disease Progression to AIDS and Death in a Rural Ugandan Cohort Is Primarily Dependent on Viral Load Despite Variable Subtype and T-Cell Immune Activation Levels
HIV-1 seroconverters from rural Uganda were evaluated to assess the effects of T-cell activation, viral load, and viral subtype on disease progression during clinical follow up. The frequency of activated T-cells was increased in HIV-1 infected Ugandans compared to community matched uninfected individuals, however there was no significant difference seen between viral subtypes. [J Infect Dis] Abstract

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1-Infected Individuals
Researchers investigated the influence of the timing of antiretroviral therapy relative to human immunodeficiency virus 1 infection on normalization of CD4⁺ T-cell counts, AIDS risk, and immune function. [JAMA Intern Med] Abstract | Editorial | Press Release

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Cocrystal Pharma and RFS Pharma Merge to Create Advanced Antiviral Development Organization
Cocrystal Pharma, Inc. announced the closing of its merger with RFS Pharma, LLC. Since 2004, RFS Pharma has been working on the development of innovative drugs to treat human viral diseases. [Cocrystal Pharma, Inc.] Press Release

bioMérieux and Illumina Enter Agreement to Co-Develop a Next-Generation Sequencing Solution for Epidemiological Monitoring of Bacterial Infections
bioMérieux and Illumina announced they have signed an exclusive agreement to launch a next-generation sequencing epidemiology solution for service labs. The two companies will jointly develop applications for microbiology sequencing technologies within a four-year renewable period. [Illumina Inc.] Press Release

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