Immunology of Infectious Disease News Volume 2.11 | Mar 26 2014

Noncanonical NF-κB Pathway Controls the Production of Type I Interferons in Antiviral Innate Immunity
Production of type I interferons (IFN-I) is a crucial innate immune mechanism against viral infections. IFN-I induction is subject to negative regulation by both viral and cellular factors, but the underlying mechanism remains unclear. Researchers report that the noncanonical NF-κB pathway was stimulated along with innate immune cell differentiation and viral infections and had a vital role in negatively regulating IFN-I induction. [Immunity] Abstract

Molecular Basis for Specific Recognition of Bacterial Ligands by NAIP/NLRC4 Inflammasomes
NLR (nucleotide-binding domain [NBD]- and leucine-rich repeat [LRR]-containing) proteins mediate innate immune sensing of pathogens in mammals and plants. How NLRs detect their cognate stimuli remains poorly understood. Here, researchers analyzed ligand recognition by NLR apoptosis inhibitory protein (NAIP) inflammasomes. [Mol Cell] Abstract | Graphical Abstract

Hepatitis B Virus Infection and Immunopathogenesis in a Humanized Mouse Model: Induction of Human-Specific Liver Fibrosis and M2-Like Macrophages
The mechanisms of chronic hepatitis B virus infection and immunopathogenesis are poorly understood due to a lack of a robust small animal model. Researchers report the development of a humanized mouse model with both human immune system and human liver cells by reconstituting the immunodeficient A2/NSG (NOD.Cg-Prkdc^scid Il2rg^tm1Wjl/SzJ mice with human HLA-A2 transgene) with human hematopoietic stem cells and liver progenitor cells. [PLoS Pathog] Full Article

Regulatory T Cells Promote a Protective Th17-Associated Immune Response to Intestinal Bacterial Infection with C. rodentium
Scientists studied the impact of Foxp3⁺ regulatory T cells (Treg) on the infectious and inflammatory processes elicited by the bacterial pathogen C. rodentium. Surprisingly, they found that depletion of Treg by diphtheria toxin in the Foxp3^DTR mouse model resulted in impaired bacterial clearance in the colon, exacerbated body weight loss, and increased systemic dissemination of bacteria. [Mucosal Immunol] Abstract

HIV

New Ex Vivo Approaches Distinguish Effective and Ineffective Single Agents for Reversing HIV-1 Latency In Vivo
Using a new ex vivo assay, researchers demonstrated that none of the latency-reversing agents (LRAs) tested induced outgrowth of HIV-1 from the latent reservoir of patients on antiretroviral therapy (ART). Using a quantitative reverse transcription PCR assay specific for all HIV-1 mRNAs, they demonstrated that LRAs that do not cause T cell activation do not induce substantial increases in intracellular HIV-1 mRNA in patient cells; only the protein kinase C agonist bryostatin-1 caused significant increases. [Nat Med] Abstract | Press Release

Stabilized Human TRIM5 Alpha Protects Human T Cells from HIV-1 Infection
Using primary human CD4 T cells, scientists investigated the ability of human (hu)TRIM5α, rhesus TRIM5α, and the huTRIM5α_R323-332 B30.2/SPRY patch-mutant to form cytoplasmic bodies, postulated as key components of the HIV-1 restriction apparatus. [Mol Ther] Abstract

Macrophage Inflammatory Markers Are Associated with Subclinical Carotid Artery Disease in Women with Human Immunodeficiency Virus or Hepatitis C Virus Infection
The macrophage inflammatory markers galectin-3-binding protein, soluble cluster of differentiation 163, and soluble cluster of differentiation 14 are significantly associated with carotid artery disease in the setting of human immunodeficiency virus and hepatitis C virus infection. [Arterioscler Thromb Vasc Biol] Abstract

HIV-1 Infection Impairs Regulatory T Cell Suppressive Capacity on a Per-Cell Basis
In vitro HIV-GFP infected and non-infected regulatory T cells (Tregs) were isolated by flow-based cell-sorting to investigate Treg suppressive capacity and gene expression profiles. Data show that HIV-1-infected Tregs were significantly less suppressive than non-infected Tregs and demonstrated down-regulation of genes critical to Treg function. [J Infect Dis] Abstract

Chemokine CXCL8 Promotes HIV-1 Replication in Human Monocyte-Derived Macrophages and Primary Microglia via Nuclear Factor-κB Pathway
Researchers investigated the effect of CXCL8 on productive infection of human immunodeficiency virus (HIV)-1 in human monocyte-derived macrophages and primary human microglia. [PLoS One] Full Article

Hepcidin and the Iron Enigma in HCV Infection
The authors discuss recent advances in the exciting crosstalk of molecular mechanisms and cell signaling pathways by which iron and hepcidin production influences HCV-induced liver disease. [Virulence]
Abstract | Full Article

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Consortium Led by Scripps Research Institute Scientist Wins Up to $28 Million from NIH to Find Best Proposed Ebola Treatment
The National Institutes of Health (NIH) has awarded a five-year grant of up to $28 million to establish a new center for excellence to find an antibody “cocktail” to fight the deadly Ebola virus. The project, which involves researchers from 15 institutions, will be led by Erica Ollmann Saphire, professor at The Scripps Research Institute. [The Scripps Research Institute] Press Release

Sanofi Pasteur Allies with SK Chemical Co. of South Korea on Pneumococcal Conjugate Vaccine
Sanofi Pasteur announced a long-term strategic cooperation with SK Chemical Co. to co-develop an innovative pneumococcal conjugate vaccine. [Sanofi Pasteur] Press Release

Breakthrough in HIV and Hep C Vaccine Research
Plans for a new type of DNA vaccine to protect against the deadly HIV and Hepatitis C viruses have taken an important step forward, with University of Adelaide researchers applying for a patent based on groundbreaking new research. Professor Gowans’ work has focused on utilizing the so-called “accessory” or “messenger” cells in the immune system, called dendritic cells, to activate an immune response. [University of Adelaide]
Press Release

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