Immunology of Infectious Disease News Volume 2.38 | Oct 1 2014

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

HIV

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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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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