Immunology of Infectious Disease News Volume 2.25 | Jul 2 2014

Dengue Virus Infection Induces Expansion of a CD14⁺CD16⁺ Monocyte Population that Stimulates Plasmablast Differentiation
Dengue virus (DENV) infection induces the expansion of plasmablasts, which produce antibodies that can neutralize DENV but also enhance disease upon secondary infection with another DENV serotype. To understand how these immune responses are generated, scientists used a systems biological approach to analyze immune responses to dengue in humans. [Cell Host Microbe] Abstract | Graphical Abstract

Activity of Broad-Spectrum T Cells as Treatment for AdV, EBV, CMV, BKV, and HHV6 Infections after Hematopoietic Stem Cell Transplantation
Scientists demonstrate the feasibility and clinical utility of rapidly generated single-culture virus-specific T cells that recognize 12 immunogenic antigens from five viruses (Epstein-Barr virus [EBV], adenovirus [AdV], cytomegalovirus [CMV], BK virus [BKV], and human herpesvirus 6 [HH6]) that frequently cause disease in immunocompromised patients. [Sci Transl Med] Abstract | Press Release | Video

HCV-Induced Immune Responses Influence the Development of Operational Tolerance after Liver Transplantation in Humans
Researchers conducted a clinical trial of immunosuppression withdrawal in hepatitis C virus (HCV)-infected adult liver recipients to elucidate the mechanisms through which allograft tolerance can be established in the presence of an ongoing inflammatory response and whether anti-HCV heterologous immune responses influence this phenomenon. [Sci Transl Med] Abstract | Press Release

Adequate Th2-Type Response Associates with Restricted Bacterial Growth in Latent Mycobacterial Infection of Zebrafish
Scientists used the Mycobacterium marinum infection model in the adult zebrafish and taken advantage of heterogeneity of zebrafish population to dissect the characteristics of adaptive immune responses, some of which are associated with well-controlled latency or bacterial clearance while others with progressive infection. [PLoS Pathog] Full Article

HIV

Specific HIV Integration Sites are Linked to Clonal Expansion and Persistence of Infected Cells
HIV integrates its DNA into many sites in the host genome; scientists identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on combination antiretroviral therapy. Approximately 50% of the infected cells in one patient were from a single clone and some clones persisted for many years. [Science] Abstract

Early Initiation of Combined Antiretroviral Therapy Preserves Immune Function in the Gut of HIV-Infected Patients
To better understand determinants of gut mucosal restoration, investigators performed phenotypic and gene expression analyses of the gut from HIV-infected patients, naïve or treated with combined antiretroviral therapy initiated either at the early phase of the primary infection or later during the chronic phase. [Mucosal Immunol] Abstract

The Presence of Anti-Tat Antibodies in HIV-Infected Individuals Is Associated with Containment of CD4⁺ T-Cell Decay and Viral Load, and with Delay of Disease Progression: Results of a 3-Year Cohort Study
Extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. Investigators showed that the presence of anti-Tat antibodies in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4⁺ T-cell loss and viral load and with a delay of disease progression. [Retrovirology]
Abstract | Full Article

miR-190b Is Markedly Upregulated in the Intestine in Response to Simian Immunodeficiency Virus Replication and Partly Regulates Myotubularin-Related Protein-6 Expression
To understand their regulatory role in the intestine, a major site of HIV/SIV replication, dissemination, and CD4⁺ T cell depletion, scientists profiled micro-RNA (miRNA) expression in colon following SIV infection. SIV infection of in vitro-cultured CD4⁺ T cells and primary intestinal macrophages conclusively identified miR-190b upregulation to be driven in response to viral replication. [J Immunol] Abstract

Prolonged Expression of an Anti-HIV-1 gp120 Minibody to the Female Rhesus Macaque Lower Genital Tract by AAV Gene Transfer
Scientists tested the hypothesis that adeno-associated virus (AAV) mediated delivery of the b12 human anti-HIV-1 gp120 minibody gene to the lower genital tract of female rhesus macaques can provide prolonged expression of b12 minibodies in the cervical-vaginal secretions. [Gene Ther] Abstract

Complexity of Cytokine Network Regulation of Innate Lymphoid Cells in Protective Immunity
The authors describe the multiple intrinsic and extrinsic pathways that comprise the cytokine circuitry regulating the development and function of innate lymphoid cells necessary for protective immunity. [Cytokine] Abstract

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GlycoVaxyn Announces the Initiation of a Phase I Clinical Trial in Collaboration with Janssen for a Vaccine against Extra-Intestinal Pathogenic Escherichia coli Causing Urinary Tract Infection
GlycoVaxyn AG announced the initiation of a Phase I clinical trial of a candidate vaccine to prevent infections caused by extra-intestinal pathogenic E. coli, such as urinary tract infections. [GlycoVaxyn AG] Press Release

Sorrento Awarded Up to $2.6 Million from the National Institutes of Health (NIH) for the Development of New Anti-Bacterial Bispecific Antibodies and Antibody Formulated Drug Conjugates
Sorrento Therapeutics, Inc. announced that it has received two NIH small business grants which will fund the development of bispecific antibodies for two of its anti-bacterial immunotherapies. [Sorrento Therapeutics, Inc.] Press Release

Bristol-Myers Squibb Receives Positive CHMP Opinion for Daklinza^® (Daclatasvir) for Treatment of Chronic Hepatitis C in the European Union
Bristol-Myers Squibb Company announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has adopted a positive opinion recommending that Daklinza^®, an investigational, potent pan-genotypic NS5A complex inhibitor (in vitro), be granted approval for use in combination with other medicinal products for the treatment of chronic hepatitis C virus infection in adults. [Bristol-Myers Squibb Company] Press Release

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NEW Postdoctoral Fellow – Sequencing Approaches with Nonhuman Primate Models of AIDS (Leidos Biomedical Research, Inc.)

Principal Investigator Positions – Systems & Synthetic Biology (Institute for Research in Immunology and Cancer)

Postdoctoral Scientist – Immune Focused In Vitro Analytics (Celentyx Ltd.)

Postdoctoral Fellow – Retroviral Evolution (Leidos Biomedical Research, Inc.)

Postdoctoral Associate – Innate Immunology/Pattern Recognition Receptor Responses and Virus-Host Interactions (Sanford Burnham Medical Research Institute)

Postdoctoral Fellow – Plasmodium/Anopheles Interactions (Fundação de Medicina Tropical Dr. Heitor Vieira Dourado)

Postdoctoral Associate – Bacterial Pathogenesis, Bioengineering and Cellular Biomechanics (Arizona State University, Biodesign Institute)

PhD Studentship – Microbiology & Immunology (INRS – University of Quebec)

Postdoctoral Position – Intestinal Mucosal Immunology and Inflammation (Universität Bern)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

Scientist – Pluripotent Stem Cell Media Development, High Throughput Screening (STEMCELL Technologies Inc.)

Scientist – Cell Culture Support Products (STEMCELL Technologies Inc.)

Scientist – Immunology/Cell Separation (STEMCELL Technologies Inc.)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

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