Immunology of Infectious Disease News Volume 3.27 | Jul 22 2015

Inhibition of Ebola Virus Glycoprotein-Mediated Cytotoxicity by Targeting Its Transmembrane Domain and Cholesterol
Researchers report that the membrane-anchored glycoprotein (GP) is sufficient to induce the detachment of adherent cells. They showed that the detachment induced through either full-length GP1,2 or the subunit GP2 depends on cholesterol and the structure of the transmembrane domain. [Nat Commun]
Abstract | Press Release

Dengue Virus Infection Elicits Highly Polarized CX3CR1⁺ Cytotoxic CD4⁺ T Cells Associated with Protective Immunity
Researchers defined HLA-restricted CD4⁺ T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4⁺ T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1⁺ Eomesodermin⁺ perforin⁺ granzyme B⁺ CD45RA⁺ CD4 CTL phenotype. [Proc Natl Acad Sci USA] Abstract

An Intranasal Virus-Like Particle Vaccine Broadly Protects Mice from Multiple Subtypes of Influenza A Virus
Scientists showed that mice were broadly protected against challenge with a wide variety of lethal influenza A virus infections with a virus-like particle vaccine cocktail. [mBio] Full Article | Press Release

Regulation of T Cell Function by MicroRNA-720
Invesitgators demonstrated that the percentage of hepatitis B virus (HBV)-specific CD8⁺ T cells is higher in the spleen of chronic HBV infection patients than that from peripheral blood and liver. miR-720 expression is upregulated in HBV-specific CD8⁺ T cells. [Sci Rep] Full Article

HIV

Antigen-Specific NK Cell Memory in Rhesus Macaques
Scientists found that splenic and hepatic natural killer (NK) cells from SHIVSF162P3-infected and SIV_mac251-infected macaques specifically lysed Gag- and Env-pulsed dendritic cells in an NKG2-dependent fashion, in contrast to NK cells from uninfected macaques. [Nat Immunol] Abstract

Vpu Exploits the Cross-Talk between BST2 and the ILT7 Receptor to Suppress Anti-HIV-1 Responses by Plasmacytoid Dendritic Cells
Investigators showed that Vpu, the HIV-1 antagonist of BST2, suppresses TLR7-mediated type-I interferon production by plasmacytoid dendritic cells through a mechanism that relies on the interaction of BST2 on HIV-producing cells with ILT7. [PLoS Pathog] Full Article | Press Release

Potent Cell-Intrinsic Immune Responses in Dendritic Cells Facilitate HIV-1-Specific T Cell Immunity in HIV-1 Elite Controllers
Scientists showed that exposure of conventional dendritic cells from elite controllers to HIV-1 leads to a rapid and sustained production of type I interferons and upregulation of several interferon-stimulated effector genes. [PLoS Pathog] Full Article | Press Release

Bryostatin Activates HIV-1 Latent Expression in Human Astrocytes through a PKC and NF-ĸB-Dependent Mechanism
To broaden the inhibitory range and effectiveness of current antiretrovirals, the potential of bryostatin was investigated as a latent HIV-1 activator. Bryostatin reactivates latent viral infection in the NHA and U87 cells via activation of protein kinase C (PKC)-alpha and -delta, because the PKC inhibitors rottlerin and GF109203X abrogated the bryostatin effect. [Sci Rep] Full Article

Langerhans Cell–Dendritic Cell Cross-Talk via Langerin and Hyaluronic Acid Mediates Antigen Transfer and Cross-Presentation of HIV-1
Investigators demonstrated that langerin not only functions as a pattern recognition receptor but also as an adhesion receptor mediating clustering between Langerhans cells and dendritic cells. [J Immunol] Abstract

Restoration of CD4⁺ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype
To better understand the dynamics of Ag-specific CD4⁺ T cells during antiretroviral therapy (ART), scientists assessed the frequency, functional capacity, and memory profile of CD4⁺ T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation [J Immunol] Abstract

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Starting Antiretroviral Treatment Early Improves Outcomes for HIV-Infected Individuals
A major international randomized clinical trial has found that HIV-infected individuals have a considerably lower risk of developing AIDS or other serious illnesses if they start taking antiretroviral drugs sooner, when their CD4⁺ T-cell count—a key measure of immune system health—is higher, instead of waiting until the CD4⁺ cell count drops to lower levels. [Press release from the National Institutes of Health discussing research presented at the 8^th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver] Press Release

Argos Therapeutics to Present at 8^th IAS Conference on HIV Pathogenesis, Treatment and Prevention
Argos Therapeutics Inc. announced Irina Tcherepanova, Ph.D. will participate in a roundtable discussion on combination therapy trials at the “Towards an HIV Cure” symposium. [Press release from Argos Therapeutics Inc. discussing research to be presented at the 8^th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver] Press Release

Novavax Announces Positive Top-Line Data from Phase I Ebola Vaccine Trial on WHO Teleconference
Novavax, Inc. announced positive top-line data from a Phase I clinical trial of its Ebola virus glycoprotein recombinant nanoparticle vaccine candidate adjuvanted with Matrix-M^™. [Press release from Novavax, Inc. discussing research presented at the World Health Organization’s (WHO) Fifth Teleconference on Ebola Vaccine Clinical Trials] Press Release

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Bristol-Myers Squibb Receives U.S. FDA Breakthrough Therapy Designation for Investigational HIV-1 Attachment Inhibitor for Heavily Treatment-Experienced Patients
Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to the investigational compound BMS-663068 when used in combination with other antiretroviral agents for the treatment of HIV-1 infection in heavily treatment-experienced adult patients. [Bristol-Myers Squibb Company] Press Release

Tekmira Provides Update on TKM-Ebola-Guinea
Tekmira Pharmaceuticals Corporation announced that the Phase II clinical trial of TKM-Ebola-Guinea has reached a predefined statistical endpoint and enrollment has been closed. [Tekmira Pharmaceuticals Corporation ] Press Release

IAS Announces 2015 CIPHER Award Grantees, Commits to Largest-Ever Grant Program in 2016
As part of its continued commitment to support young and emerging investigators and address priority research gaps in paediatric HIV, the International AIDS Society (IAS) announced its 2015 award winners for the IAS Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) Grant Program. [International AIDS Society] Press Release

Scripps Florida Scientists Receive $2.8 Million to Develop Innovative Approach to Latent HIV Infection
A team of scientists from the Scripps Research Institute in Jupiter received $2.8 million in grants to develop an HIV treatment. [Scripps Research Institute] Press Release

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