Volume 2.38 | Oct 1

Immunology of Infectious Disease News 2.38 October 1, 2014
Immunology of Infectious Disease News
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Yerkes Researchers First to Show Irradiation Plus Transplantation Effective for Treating HIV/AIDS
Yerkes National Primate Research Center researchers are the first to show that an irradiation plus transplantation combination approach in nonhuman primates can be used to treat or even possibly cure HIV/AIDS, and this new model is providing some answers about the “Berlin patient,” the only human thought cured of AIDS. [Press release from Emory University discussing online publication in PLoS Pathogens]
Press Release
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Toso Regulates Differentiation and Activation of Inflammatory Dendritic Cells during Persistence-Prone Virus Infection
Scientists used the lymphocytic choriomeningitis virus model system to identify novel signals, which influence the recruitment and activation of inflammatory dendritic cells (iDCs) in the liver. They observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. [Cell Death Differ] Abstract

CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression
The authors evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. They show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160+ CD8 T cells may be independent of PD-1 expression. [PLoS Pathog]
Full Article

Pathogenic IgG Antibodies against Desmoglein 3 in Pemphigus Vulgaris Are Regulated by HLA-DRB1*04:02-Restricted T Cells
Investigators show in a humanized HLA-DRB1*04:02-transgenic mouse model that HLA-DRB1*04:02-restricted T cell recognition of human desmosomal cadherin desmoglein 3 epitopes leads to the induction of pathogenic IgG Abs that induce loss of epidermal adhesion, a hallmark in the immune pathogenesis of pemphigus vulgaris. [J Immunol] Abstract

Impaired Gamma Delta T Cell-Derived IL-17A and Inflammasome Activation during Early Respiratory Syncytial Virus Infection in Infants
Using a neonatal mouse model of respiratory syncytial virus (RSV), researchers demonstrate that neonates fail to develop interleukin (IL)-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. [Immunol Cell Biol] Abstract


Casp8p41 Generated by HIV Protease Kills CD4 T Cells through Direct Bak Activation
Human immunodeficiency virus (HIV) protease cleaves procaspase 8 to a fragment, termed Casp8p41, that lacks caspase activity but nonetheless contributes to T cell apoptosis. The authors show that Casp8p41 contains a domain that interacts with the BH3-binding groove of pro-apoptotic Bak to cause Bak oligomerization, Bak-mediated membrane permeabilization, and cell death. [J Cell Biol] Abstract

Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3
Researchers investigated antiviral and inflammatory responses induced in human immature dendritic cells after exposure to free HIV-1, complement-opsonized HIV-1, and complement and Ab-opsonized HIV-1. [J Immunol] Abstract | Full Article

Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages
Scientists examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. [PLoS One] Full Article

CCR5 Gene Editing of Resting CD4+ T Cells by Transient ZFN Expression from HIV Envelope Pseudotyped Nonintegrating Lentivirus Confers HIV-1 Resistance in Humanized Mice
Investigators used non-integrating lentivirus (NILV) for transient expression of zinc finger nucleases (ZFNs) and pseudotyped the virus with HIV-envelope for targeted delivery to CD4+ T cells. Both activated and resting primary CD4+ T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro.
[Mol Ther Nucleic Acids]
Full Article

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A Roadmap toward Clinical Translation of Genetically-Modified Stem Cells for Treatment of HIV
The authors outline a high level roadmap for the early stage development of hematopoietic stem cell (HSC) gene therapy as a potential functional cure for HIV [Trends Mol Med] Abstract

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Mymetics’ Promising HIV Vaccine Candidate Obtains Funding to Begin Study at Texas Biomedical Research Institute
Mymetics Corporation, a pioneer in the research and development of virosome-based vaccines to prevent transmission of human infectious diseases across mucosal membranes, announced that its HIV vaccine candidate will enter a new preclinical trial to confirm results obtained in a previous trial. [Mymetics Corporation] Press Release

Inovio Pharmaceuticals Ebola Vaccine Moving into Human Trial with GeneOne Life Science
Inovio Pharmaceuticals, Inc. announced it will advance its DNA vaccine for Ebola into a Phase I clinical trial in a collaboration with GeneOne Life Science Inc. [Inovio Pharmaceuticals, Inc.] Press Release

Gilead’s Investigational Tenofovir Alafenamide (TAF)-Based Single Tablet HIV Regimen Meets 48-Week Primary Objective in Two Phase III Studies
Gilead Sciences, Inc. announced that two Phase III clinical trials evaluating an investigational once-daily single tablet regimen containing tenofovir alafenamide for the treatment of HIV-1 infection in treatment-naïve adults met their primary objectives. [Gilead Sciences, Inc.] Press Release

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