Volume 1.06 | Apr 24

Immunology of Infectious Disease News 1.06 April 24, 2013
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TOP STORY
Distinct Memory CD4+ T Cells with Commitment to T Follicular Helper- and T Helper 1-Cell Lineages Are Generated after Acute Viral Infection
Using adoptive transfer of antigen-specific memory CD4+ T cell subpopulations in the lymphocytic choriomeningitis virus infection model, the authors found that there are distinct memory CD4+ T cell populations with commitment to either T follicular helper- or T helper 1-cell lineages. Their findings indicate that CD4+ memory T cells remember their previous effector lineage after antigen clearance, being poised to reacquire their lineage-specific effector functions upon antigen reencounter. [Immunity]
Abstract | Graphical Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

Increased CD8+ T Cell Response to Epstein-Barr Virus Lytic Antigens in the Active Phase of Multiple Sclerosis
Researchers assessed the prevalence and magnitude of CD8+ T-cell responses to Epstein-Barr virus (EBV) latent and lytic antigens in relapsing-remitting multiple sclerosis patients and healthy donors and investigated whether the EBV-specific CD8+ T cell response correlates with disease activity, as defined by clinical evaluation and gadolinium-enhanced magnetic resonance imaging. [PLoS Pathog] Full Article

Both TRIF and IPS-1 Adaptor Proteins Contribute to the Cerebral Innate Immune Response against HSV-1 Infection
Toll-like receptors (TLRs) and RNA helicases (RLHs) are important cell sensors involved in the immunological control of viral infections through production of type 1 interferon. The impact of a deficiency in TRIF and IPS-1 adaptor proteins, respectively implicated in TLR3 and RLHs signaling pathways, was investigated during herpes simplex virus type 1 (HSV-1) encephalitis. [J Virol] Abstract

Suppressed Th17 Levels Correlate with Elevated PIAS3, SHP2, and SOCS3 Expression in CD4 T Cells during Acute Simian Immunodeficiency Virus Infection
Using ex vivo analysis of purified peripheral blood CD4 T cells from simian immunodeficiency virus infected rhesus macaques, the authors showed that the suppression of IL-17 expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed T helper 17 (Th17) expression was accompanied by elevated levels of soluble CD14 and LPS binding protein in the plasma during early stages of infection. [J Virol] Abstract

Unique Transcriptional Profile of Liver-Resident Memory CD8+ T Cells Induced by Immunization with Malaria Sporozoites
The authors characterized and compared the transcriptional profile of parasite-specific memory CD8+ T cells residing in the liver and spleen after immunization of mice with irradiated sporozoites. [Genes Immun] Abstract

Virus-Induced CD8+ T Cells Accelerate the Onset of Experimental Autoimmune Encephalomyelitis: Implications for How Viral Infections Might Trigger Multiple Sclerosis Exacerbations
Scientists developed an experimental system whereby infection with an asymptomatic neurotropic alphavirus caused a transient acceleration of experimental autoimmune encephalomyelitis without altering the expansion or differentiation of autoreactive CD4+ T cells. [J Neuroimmunol] Abstract

HIV

The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity, Is Regulated by Phosphorylation
Researchers determined that SAMHD1 is phosphorylated on residue T592 in cycling cells but that this phosphorylation is lost when cells are in a noncycling state. Reverse genetic experiments revealed that SAMHD1 phosphorylated on residue T592 is unable to block retroviral infection, but this modification does not affect the ability of SAMHD1 to decrease cellular deoxynucleoside triphosphates levels. [Cell Host Microbe] Full Article | Press Release

Interferon-Inducible Mechanism of Dendritic Cell-Mediated HIV-1 Dissemination Is Dependent on Siglec-1/CD169
Scientists demonstrated that the type I IFN-inducible Siglec-1, CD169, is the dendritic cell (DC) receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of glycosphingolipids (GSLs) from virions, abrogated DC-mediated human immunodeficiency virus type 1 (HIV-1) capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. [PLoS Pathog] Full Article

The Infectious Synapse Formed between Mature Dendritic Cells and CD4+ T Cells Is Independent of the Presence of the HIV-1 Envelope Glycoprotein
Investigators explored the contribution of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein, adhesion molecules, and antigen recognition in the formation of conjugates comprising mature DC (mDC) and CD4+ T cells in order to further evaluate their role in mDC-mediated HIV-1 transmission at the immunological synapse. [Retrovirology] Abstract | Full Article

The Magnitude of HIV-1 Resistance to the CCR5 Antagonist Maraviroc May Impart a Differential Alteration in HIV-1 Tropism for Macrophages and T-Cell Subsets
The authors characterized tropism alterations for CD4+ T-cell subsets and macrophages by envelope glycoproteins from two subjects who developed maraviroc (MVC) resistance in vivo, which displayed either relatively efficient or inefficient recognition of MVC-bound CCR5. [Virology] Abstract

Phosphorylation of SAMHD1 by Cyclin A2/CDK1 Regulates Its Restriction Activity toward HIV-1
SAMHD1 restricts HIV-1 replication in myeloid and quiescent CD4+ T cells. Here, investigators showed that SAMHD1 restriction activity is regulated by phosphorylation. SAMHD1 interacts with cyclin A2/cdk1 only in cycling cells. Cyclin A2/CDK1 phosphorylates SAMHD1 at the Thr592 residue both in vitro and in vivo. [Cell Rep] Full Article | Graphical Abstract

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REVIEWS

Understanding Immunosenescence to Improve Responses to Vaccines
Most insights into mechanisms of immunological aging have been derived from studies of mouse models. The authors explore how well such models are applicable to understanding the aging process throughout the 80-100 years of human life and discuss recent advances in identifying and characterizing the mechanisms that underlie age-associated defective adaptive immunity in humans. [Nat Immunol] Abstract

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

SCIENCE NEWS
High Rates of SVR Demonstrated in Phase II Study with Investigational Triple DAA Regimen of Daclatasvir, Asunaprevir and BMS-791325 in Treatment-Naïve Patients with Genotype 1 Chronic Hepatitis C Infection
Bristol-Myers Squibb Company announced additional, interim Phase II data demonstrating that 12- and 24-week Triple DAA treatment regimens of daclatasvir, asunaprevir and BMS-791325 achieved high rates of sustained virologic response (SVR) of up to 94%, in treatment-naïve, genotype 1 chronic hepatitis C patients, at time points ranging from 4 to 36 weeks post-treatment depending on the treatment group. [Press release from Bristol-Myers Squibb Company discussing research to be presented at the International Liver Congress, the 48th Annual Meeting of the European Association for the Study of the Liver (EASL), Amsterdam]
Press Release

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INDUSTRY NEWS

U of M Researchers Conduct World’s First Cord Blood Transplant Aimed at Curing Leukemia and HIV/AIDS
University of Minnesota (U of M) physicians will perform the world’s first cord blood transplant designed specifically to cure a pediatric patient of HIV/AIDS and acute lymphoblastic leukemia. [University of Minnesota] Press Release

Immune Targeting Systems Announces Positive Phase IIa Data in the At Risk Elderly Population with Flunisyn™, Its Pan-Strain Onfluenza A T-Cell Vaccine, and Two UK Biomedical Catalyst Grants for Chronic Hepatitis B and Oncology

Immune Targeting Systems Limited (ITS), announced positive data from a Phase IIa trial with the Company’s lead pan-strain influenza A T-cell vaccine, FlunisynTM, in the elderly population. An emerging leader in the development of T-cell vaccines against viruses and cancers, ITS also announced two major grant awards from the UK’s Biomedical Catalyst funding scheme to develop chronic hepatitis B vaccine and oncology vaccine product candidates. [Immune Targeting Systems Limited] Press Release

International Prize for Mizrahi’s Research and Mentoring
The €500,000 award, made by the Institute’s Academy of Sciences, is a highly prestigious international accolade and will be presented to Mizrahi at a ceremony in Paris. The Academy of Sciences, which makes awards to the most meritorious scientists and promising research projects, also lauded Mizrahi for her special qualities in mentoring students, particularly those engaged in tuberculosis research. [University of Cape Town] Press Release

POLICY NEWS

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)

EVENTS

NEW Molecular Basis of Bacterial Infection: Contemporary Research Approaches
May 12-18, 2013
Cambridge, United Kingdom

NEW
Retroviruses
May 20-25, 2013
Cold Spring Harbor, United States

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

JOB OPPORTUNITIES

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)

Director – Basic Sciences Program (National Institute of Allergy and Infectious Disease/National Institutes of Health)

Postdoctoral Position – Synthetic Biology, RNAi & Gene Therapy (University of Heidelberg Medical School)

Assistant Scientist (University of Wisconsin – Madison Primate Research Center)

Research Associate – Infection and Immunity (Cardiff University)


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