Immunology of Infectious Disease News Volume 1.11 | May 29 2013

Cytomegalovirus Vectors Violate CD8⁺ T Cell Epitope Recognition Paradigms
Scientists found that simian immunodeficiency virus (SIV) protein-expressing rhesus cytomegalovirus vectors elicit SIV-specific CD8⁺ T cells that recognize unusual, diverse, and highly promiscuous epitopes, including dominant responses to epitopes restricted by class II major histocompatibility complex molecules. [Science] Abstract | Press Release

PUBLICATIONS (Ranked by impact factor of the journal)

Inflammatory Monocytes Regulate Pathologic Responses to Commensals during Acute Gastrointestinal Infection
Scientists showed that during acute mucosal infection of mice with Toxoplasma gondii, inflammatory monocytes acquire a tissue-specific regulatory phenotype associated with production of the lipid mediator prostaglandin E₂. [Nat Med] Abstract | Press Release 

Differentiation of CD8 Memory T Cells Depends on Foxo1
Naive antigen-specific CD8⁺ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure. In addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. Using lymphocytic choriomeningitis virus Armstrong to probe the response to infection, the authors found that forkhead O transcription factors 1 (Foxo1)^–/- CD8⁺ T cells expand normally with no defects in effector differentiation, but continue to exhibit characteristics of effector T cells long after antigen clearance. [J Exp Med] Abstract

Harnessing Alveolar Macrophages for Sustained Mucosal T-Cell Recall Confers Long-Term Protection to Mice against Lethal Influenza Challenge without Clinical Disease
Investigators describe intranasal immunization of mice with a lentiviral vector expressing influenza nucleoprotein (NP), together with an NFκB activator, which transduces over 75% of alveolar macrophages. This strategy recalls and expands NP-specific CD8+ T cells in the lung and airway of mice that have been immunized subcutaneously, or previously exposed to influenza. [Mucosal Immunol] Abstract

Helicobacter pylori Infection Inhibits Phagocyte Clearance of Apoptotic Gastric Epithelial Cells
To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, the authors investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. [J Immunol] Abstract

Detection of JC Virus-Specific Immune Responses in a Novel Humanized Mouse Model
Mice were inoculated with either a progressive multifocal leukoencephalopathy isolate, JC virus (JCV) Mad-4, or with JCV CY, found in the kidney and urine of healthy individuals. Mice generated both humoral and cellular immune responses against JCV. [PLoS One] Full Article

HIV

A Single Amino-Acid Change in a Highly Conserved Motif of gp41 Elicits HIV-1 Neutralization and Protects against CD4 Depletion
In vivo, anti-3S antibodies protect against the NK-cell mediated CD4 depletion that occurs without efficient viral neutralization. Investigators showed that specific substitutions in the 3S motif reduce viral infection without affecting gp41 production, while decreasing both its capacity to induce NKp44 L expression on CD4⁺ T cells and its sensitivity to autologous NK cells. [Clin Infect Dis] Abstract

GB Virus C Particles Inhibit T Cell Activation via Envelope E2 Protein-Mediated Inhibition of TCR Signaling
GB virus C (GBV-C) infection is associated with reduced T cell activation in HIV-infected humans, and immune activation is a critical component of HIV disease pathogenesis. Scientists demonstrated that serum GBV-C particles inhibited activation of primary human T cells. T cell activation inhibition was mediated by the envelope glycoprotein E2, because expression of E2 inhibited TCR-mediated activation of Lck. [J Immunol] Abstract

Decreased Frequency of CD73⁺CD8⁺ T Cells of HIV-Infected Patients Correlates with Immune Activation and T Cell Exhaustion
Researchers analyzed the expression of CD73 on peripheral and lymph nodal Teffs and Tregs in a cohort of 95 HIV patients at different stages of disease, including LTNP and ECs. In contrast to murine Tregs, CD73 was only expressed on a small minority of peripheral Tregs. In contrast, they saw high expression of CD73 on peripheral CD8⁺ T cells. [J Leukoc Biol] Abstract

Some Mechanisms of FLIP Expression in Inhibition of HIV-1 Replication in Jurkat Cells, CD4+ T Cells and PBMCs
Using the susceptible Jurkat cell line, CD4+ T cells, and peripheral blood mononuclear cells (PBMCs), the authors studied the role of FLIP, an inhibitor of caspase-8, in HIV-1 production. [J Cell Physiol] Abstract

Polyfunctional CD4⁺ T Cell Responses in HIV-1-Infected Viral Controllers Compared with Those in Healthy Recipients of an Adjuvanted Polyprotein HIV-1 Vaccine
A recombinant fusion protein consisting of HIV-1 p17, p24, reverse transcriptase and Nef, adjuvanted with AS01, induced strong and broad CD4⁺ T-cell responses in healthy volunteers. Scientists compared these vaccine-induced CD4⁺ T-cell responses with the ones induced by natural infection in patients with varying disease courses. [Vaccine] Abstract

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Iron in Infection and Immunity
Given the absolute requirement for iron by virtually all human pathogens, an important facet of the innate immune system is to limit iron availability to invading microbes in a process termed nutritional immunity. Successful human pathogens must therefore possess mechanisms to circumvent nutritional immunity in order to cause disease. This review discusses regulation of iron metabolism in the setting of infection and delineate strategies used by human pathogens to overcome iron-withholding defenses. [Cell Host Microbe] Abstract

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

Spring Bank Pharmaceuticals Initiates a Phase I Clinical Trial for SB 9200 in HCV-infected Patients
Spring Bank Pharmaceuticals, Inc. announced that it has initiated dosing in a Phase I study of SB 9200, its investigational, once daily, oral therapy for the treatment of HCV infection. This study will be conducted in healthy, HCV-infected patients and is designed to assess both the safety and antiviral efficacy of SB 9200. [Spring Bank Pharmaceuticals, Inc.] Press Release

Dr. Jewett Receives Highly Competitive NIH Research Grant
Dr. Mollie Jewett has received a RO1 grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) for her work in the prevention and treatment of Lyme disease. The NIH provided the total $1.2 million grant for four years. RO1 or Research Project Grants provide support for health-related research by a sole investigator that addresses a public health need with an innovative approach. [University of Central California College of Medicine] Press Release

Cempra Awarded $58 Million Contract to Develop Antibiotic for Pediatric Use and Biodefense by Biomedical Advanced Research and Development Authority (BARDA)
Cempra, Inc. announced that the BARDA has awarded Cempra with a five year contract valued up to $58 million for the development of solithromycin to treat infections in pediatric populations and for the treatment of infections by bioterror threat pathogens. Solithromycin is a fourth generation macrolide antibiotic in the fluoroketolide family that is currently in Phase III development for community-acquired bacterial pneumonia in adults. [Cempra, Inc.] Press Release

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Canada Research Chair – Immunology of Chronic Viral Infections & Immune Senescence (Dalhousie University Faculty of Medicine)

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