Immunology of Infectious Disease News Volume 1.03 | Apr 3 2013

PUBLICATIONS (Ranked by impact factor of the journal)

Treatment of HCV Infection by Targeting MicroRNA
In this phase IIa study at seven international sites, researchers evaluated the safety and efficacy of miravirsen in 36 patients with chronic hepatitis C virus (HCV) genotype 1 infection. The patients were randomly assigned to receive five weekly subcutaneous injections of miravirsen or placebo over a 29-day period. They were followed until 18 weeks after randomization.[N Engl J Med] Full Article | Press Release

Discovering Naturally Processed Antigenic Determinants that Confer Protective T Cell Immunity
The authors employed a proteomics-based approach for large-scale discovery of naturally processed determinants derived from a complex pathogen, vaccinia virus (VACV), that are presented by the most frequent representatives of four major HLA class I supertypes. Immunologic characterization revealed that many previously unidentified VACV determinants were recognized by smallpox-vaccinated human peripheral blood cells in a variegated manner. [J Clin Invest] Full Article

Biomimetic Antigenic Nanoparticles Elicit Controlled Protective Immune Response to Influenza
Researchers present a biomimetic strategy for nanoparticle design for controlled immune response through encapsulation of conserved internal influenza proteins on the interior of virus like particles to direct CD8+ cytotoxic T cell protection. [ACS Nano] Abstract

Hepatitis C Virus NS4B Blocks the Interaction of STING and TBK1 to Evade Host Innate Immunity
Scientists explored a novel NS3/4A-independent mechanism that hepatitis C virus (HCV) utilizes to evade host innate immune responses. They report an additional mechanism for HCV evasion of host interferon responses in which viral NS4B protein targets STING/MITA to suppress the interferon signaling. [J Hepatol] Abstract

CD8⁺ T Cell Activation by Murine Erythroblasts Infected with Malaria Parasites
Researchers generated a rodent malaria parasite (P. yoelii 17XNL) expressing GFP-ovalbumin. Its infectivity to erythroblasts was confirmed, and parasitized erythroblasts were capable of initiating malaria infections. Experiments showed that MHC class I molecules were highly expressed on parasitized erythroblasts. As CD8⁺ T cells recognize MHC class I and peptide complexes on target cells, and are involved in protection or pathology against malaria, the authors examined whether erythroblasts are targeted by CD8⁺ T cells. [Sci Rep]
Full Article

HIV

Somatic Mutations of the Immunoglobulin Framework Are Generally Required for Broad and Potent HIV-1 Neutralization
Investigators report that in contrast to most antibodies, including those with limited HIV-1 neutralizing activity, most broadly neutralizing antibodies require somatic mutations in their framework regions (FWRs). Structural and functional analyses revealed that somatic mutations in FWR residues enhance breadth and potency by providing increased flexibility and/or direct antigen contact. [Cell]
Abstract | Graphical Absract | Press Release

Phenotypic Properties of Transmitted Founder HIV-1
The authors generated infectious molecular clones of transmitted founder (TF) and chronic control (CC) viruses of subtypes B and C and compared their phenotypic properties in assays specifically designed to probe the earliest stages of HIV-1 infection. They found that TF virions were 1.7-fold more infectious and contained 1.9-fold more envelope per particle compared with CC viruses. TF viruses were also captured by monocyte-derived dendritic cells 1.7-fold more efficiently and more readily transferred to CD4+ T cells. [Proc Natl Acad Sci USA] Abstract | Press Release

HIV Restriction by APOBEC3 in Humanized Mice
Researchers demonstrated that apolipoprotein B mRNA editing enzyme catalytic polypeptide 3 (APOBEC3) efficiently restricts CCR5-tropic human Immunodeficiency virus (HIV) in the absence of viral infectivity factor (Vif). However, their results also showed that CXCR4-tropic HIV can escape from APOBEC3 restriction and replicate in vivo independent of Vif. [PLoS Pathog] Full Article | Press Release

Microbial Translocation Induces an Intense Proinflammatory Response in Visceral Leishmaniasis Patients Co-infected with HIV-1
Leishmania infection is a co-factor in the heightened cellular activation observed in American visceral leishmaniasis-HIV-1/AIDS patients (AVL/HIV-1). Thus, the persistence of a high parasite load despite anti-leishmanial therapy could be responsible for the continued immune stimulation. CD8⁺T cells expressing CD38, parasite load, lipopolysaccharide, soluble CD14, macrophage migration inhibitory factor, intestinal fatty acid-binding protein and proinflammatory cytokines were measured in 17 AVL/HIV-1, 16 HIV-1/AIDS patients and 14 healthy subjects. [J Infect Dis] Abstract

Immunohistological Characterization of Spinal TB Granulomas from HIV-Negative and -Positive Patients
Scientists examined the histopathology and distribution of immune cells within spinal tuberculosis (TB) lesions and the impact of HIV on pathogenesis. The overall structure of the spinal granulomas resembled that seen in lung lesions from patients with pulmonary TB. Evidence of efficient macrophage activation and differentiation were detectable within organized structures in the spinal tissue, irrespective of HIV status. [Tuberculosis] Abstract

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Barriers to a Cure for HIV: New Ways to Target and Eradicate HIV-1 Reservoirs
The authors look at new approaches to unraveling the complex virus-host interactions that lead to persistent infection and latency, and discuss the rationale for combination of novel treatment strategies with available antiretroviral treatment options to cure HIV. [Lancet] Abstract 

Visit our reviews page to see a complete list of reviews in the infectious disease research field.

National Institutes of Health Awards $1.5 Million to University of Georgia Researchers Studying Legionnaires’ Disease
University of Georgia researcher Vincent Starai was recently awarded $1,503,565 by the National Institutes of Health to investigate how the bacterium that causes Legionnaires’ disease, Legionella pneumophila, overcome the body’s defenses. [University of Georgia] Press Release

Biologist Earns $1.6 Million National Institutes of Health Grant
A Texas Tech University biology professor received a five-year, $1.6 million grant from the National Institutes of Health to study the biochemistry of a microscopic parasite responsible for the tropical disease leishmaniasis in the hope of finding a cure. [Texas Tech University] Press Release

Grant: Cooperative Centers on Human Immunology (U19)
The purpose of this Funding Opportunity is to support hypothesis-testing, mechanistic studies on the activation and regulation of human immune responses in the context of infectious disease. This research program was initiated by National Institute of Allergy and Infectious Diseases in fiscal year 2003 and is being renewed for the second time through open competition. [National Institutes of Health] Link

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW Cold Spring Harbor Asia: Vaccine Design
June 3-7, 2013
Suzhou, China

Visit our events page to see a complete list of events in the infectious disease community.

PhD Studentship – Vaccine Development for Bacterial Infectious Disease (University of Calgary, Department of Production Animal Health)

Director – Vaccine Research Center (National Institute of Allergy and Infectious Diseases)

Postdoctoral Fellow – Immunology (California Institute for Biomedical Research)

Postdoctoral Fellow (Columbia Initiative for Systems Biology / Columbia University)

Postdoctoral Fellows (Louisiana State University (LSU))

Postdoctoral Position – Immunology and Vaccinology (Université de Liège)

Postdoctoral Position – Immunology (New York University)

Postdoctoral Scientist (National Institute for Medical Research, Medical Research Council)

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