STAT1-Cooperative DNA Binding Distinguishes Type 1 from Type 2 Interferon Signaling To investigate the importance of STAT1-cooperative DNA binding, investigators generated gene-targeted mice expressing cooperativity-deficient STAT1 with alanine substituted for Phe77. Neither ISGF3 nor GAF bound DNA cooperatively in the STAT1F77A mouse strain, but type 1 and type 2 interferon responses were affected differently. [Nat Immunol] Abstract | Press Release Human Natural Killer Cells Control Plasmodium falciparum Infection by Eliminating Infected Red Blood Cells The authors showed that the adhesion molecule lymphocyte-associated antigen 1 is required for natural killer cell interaction with and elimination of infected red blood cells. [Proc Natl Acad Sci USA] Abstract | Press Release Leukocyte Immunoglobulin-Like Receptor B1 Is Critical for Antibody-Dependent Dengue The enhancement of dengue virus (DENV) infection is curious as cross-linking of activating Fc-gamma receptors (FcγRs) signals an early antiviral response by inducing the type-I IFN-stimulated genes (ISGs). Entry through activating FcγR would thus place DENV in an intracellular environment unfavorable for enhanced replication. Researchers demonstrated that, to escape this antiviral response, antibody-opsonized DENV coligates leukocyte Ig-like receptor-B1 to inhibit FcγR signaling for ISG expression. [Proc Natl Acad Sci USA] Abstract | Press Release T-bet Regulates Immunity to F. tularensis LVS Infection, Particularly in Lungs Upregulation of the transcription factor T-bet is correlated with strength of protection against secondary challenge with the Live Vaccine Strain (LVS) of Francisella tularensis, which causes the highly infectious disease tularemia. To determine if this mediator had direct consequences in immunity to LVS, investigators examined its role in infection. [Infect Immun] Abstract HIV Premature Activation of the SLX4 Complex by Vpr Promotes G2/M Arrest and Escape from Innate Immune Sensing Investigators showed that the SLX4 complex is involved in suppressing spontaneous and HIV-1-mediated induction of type 1 interferon and establishment of antiviral responses. [Cell] Abstract | Graphical Abstract HIV-1 Persistence in CD4+ T Cells with Stem Cell-Like Properties Researchers showed that during suppressive antiretroviral therapy, CD4+ T memory stem cells harbor high per-cell levels of HIV-1 DNA and make increasing contributions to the total viral CD4+ T cell reservoir over time. [Nat Med] Abstract | Press Release Targeted Cytotoxic Therapy Kills Persisting HIV Infected Cells During ART For targeted cytotoxic killing of persistent vRNA+ cells, the authors treated bone marrow-liver-thymus mice undergoing antiretroviral therapy (ART) with an HIV-specific immunotoxin. They found that compared to ART alone, this agent profoundly depleted productively infected cells systemically. [PLoS Pathog] Full Article | Press Release HIV-1 Triggers WAVE2 Phosphorylation in Primary CD4 T Cells and Macrophages, Mediating Arp2/3-Dependent Nuclear Migration Scientists report that HIV-1 triggers WAVE2 phosphorylation at serine 351 through gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry. This phosphorylation event involves both Gαi-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages. [J Biol Chem] Abstract | Full Article A Parameter for IL-10 and TGF-ß Mediated Regulation of HIV-1 Specific T Cell Activation Provides Novel Information and Relates to Progression Markers The authors explored a quantitative parameter for antigen-induced cytokine-mediated regulation of HIV-specific effector T cell activation by functional antibody-blockade of IL-10 and transforming growth factor-β. [PLoS One] Full Article |