Immunology of Infectious Disease News Volume 2.27 | Jul 16 2014

Measles Virus Suppresses RIG-I-Like Receptor Activation in Dendritic Cells via DC-SIGN-Mediated Inhibition of PP1 Phosphatases
Researchers demonstrate that measles virus suppresses RIG-I and Mda5 by activating the C-type lectin DC-SIGN and inducing signaling that prevents RIG-I-like receptor dephosphorylation. [Cell Host Microbe]
Abstract | Graphical Abstract | Press Release

A BTLA-Mediated Bait and Switch Strategy Permits Listeria Expansion in CD8α⁺ DCs to Promote Long-Term T Cell Responses
Researchers found that activating the B and T lymphocyte attenuator (BTLA), a coinhibitory receptor for T cells, suppresses, while blocking BTLA enhances, both the primary and memory CD8 T cell responses against Listeria monocytogenes. [Cell Host Microbe] Abstract | Graphical Abstract

Commensal Microbes Drive Intestinal Inflammation by IL-17-Producing CD4⁺ T Cells through ICOSL and OX40L Costimulation in the Absence of B7-1 and B7-2
Investigators show that B7 deprivation in mice overrides the necessity for regulator T cells (Tregs) in averting systemic autoimmunity and inflammation in extraintestinal tissues, whereas peripherally induced Tregs retained in the absence of B7 selectively mitigate intestinal inflammation caused by Th17 effector CD4⁺ T cells. [Proc Natl Acad Sci USA] Abstract

Distinct Lipid A Moieties Contribute to Pathogen-Induced Site-Specific Vascular Inflammation
Scientists utilized a series of Porphyromonas gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade Toll-like receptor-4-mediated bactericidal activity in macrophages resulting in systemic inflammation. [PLoS Pathog] Full Article | Press Release

Pneumolysin Expression by Streptococcus pneumoniae Protects Colonized Mice from Influenza Virus-Induced Disease
Using mutant S. pneumoniae (Sp) strains, researchers identified a critical role for the bacterial virulence factor pneumolysin (PLY) in mediating protection. Colonization with the PLY-sufficient Sp strain induces expression of the immune-suppressive enzyme arginase 1 in alveolar macrophages and correlates with attenuated recruitment and function of pulmonary inflammatory cells. [Virology] Full Article | Press Release

HIV

Type I Interferon Responses in Rhesus Macaques Prevent SIV Infection and Slow Disease Progression
Scientists manipulated interferon (IFN)-I signaling in rhesus macaques during simian immunodeficiency virus (SIV) transmission and acute infection with two complementary in vivo interventions. They show that blockade of the IFN-I receptor caused reduced antiviral gene expression, increased SIV reservoir size and accelerated CD4 T-cell depletion with progression to AIDS despite decreased T-cell activation. [Nature] Abstract

Proliferation of Cells with HIV Integrated into Cancer Genes Contributes to Persistent Infection
Researchers evaluated the contribution of infected-cell proliferation and sites of proviral integration to HIV persistence. Each participant had identical viral sequences integrated at the same position in multiple cells, demonstrating infected-cell proliferation. [Science] Abstract

Deficient Synthesis of Class-Switched, HIV-Neutralizing Antibodies to the CD4⁺ Binding Site and Correction by Electrophilic gp120 Immunogen
Serum antibody responses to a linear CD4⁺ binding site epitope of gp120 peptide and full-length gp120 epitopes induced by HIV infection in humans and immunization of mice with gp120 or E-gp120 were monitored. HIV neutralization by monoclonal and variable domain-swapped antibodies was determined from tissue culture and humanized mouse infection assays. [AIDS] Abstract

Cutting Edge: An Antibody Recognizing Ancestral Endogenous Virus Glycoproteins Mediates Antibody-Dependent Cellular Cytotoxicity on HIV-1-Infected Cells
Scientists demonstrate that a human anti-human endogenous retroviral-K transmembrane protein Ab binds specifically to HIV-1-infected cells and eliminates them through an Ab-dependent cellular cytotoxicity mechanism in vitro. [J Immunol] Abstract | Full Article

IL-10 and Lymphotoxin-α Expression Profiles within Marginal Zone-Like B-Cell Populations Are Associated with Control of HIV-1 Disease Progression
Investigators report that although B-cell dysregulations associated with HIV-1 disease progression are accompanied by an overall decrease in the percentage of total blood B-cells, they observed an increase in relative frequencies of cells presenting characteristics of both transitional immature and first-line marginal zone B-cell populations. [PLoS One] Full Article

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Hemispherx Biopharma and Bioclones Join Forces in Effort to Eradicate HIV/AIDS Virus Based on Recent Clinical Insights of Wistar Institute, University of Pennsylvania
Hemispherx Biopharma, Inc. announced execution of an agreement to seek South African government approval to initiate a study of Alferon^® N, the only FDA approved natural interferon, in the suppression of HIV Type 1 replication and the reduction/elimination of functional cell-associated HIV DNA integration. [Hemispherx Biopharma, Inc.] Press Release

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