Immunology of Infectious Disease News Volume 2.06 | Feb 19 2014

Interferon Lambda Alleles Predict Innate Antiviral Immune Responses and Hepatitis C Virus Permissiveness
Using a laser capture microdissection-driven unbiased systems virology approach, scientists isolated and transcriptionally profiled Hepatitis C virus (HCV)-infected and adjacent primary human hepatocytes approaching single-cell resolution. An innate antiviral immune signature dominated the transcriptional response but differed in magnitude and diversity between HCV-infected and adjacent cells. [Cell Host Microbe]
Full Article | Graphical Abstract

Toll-Like Receptor-Deficient Mice Reveal How Innate Immune Signaling Influences Salmonella Virulence Strategies
Researchers evaluated Salmonella enterica serovar Typhimurium (ST) virulence in mice lacking all toll-like receptor (TLR) function. When delivered systemically to TLR-deficient mice, ST do not require Salmonella pathogenicity island 2 and maintain virulence by replicating extracellularly. [Cell Host Microbe]
Abstract | Graphical Abstract

Quantitative and Qualitative Deficits in Neonatal Lung-Migratory Dendritic Cells Impact the Generation of the CD8+ T Cell Response
Researchers compared the responses of two dendritic cell (DC) populations in neonatal and adult mice following intranasal infection with respiratory syncytial virus. The response in neonates was dominated by functionally-limited CD103+ DCs, while CD11b+ DCs were diminished in both number and function compared to adults. [PLoS Pathog] Full Article | Press Release

Dendritic Cells Coordinate Innate Immunity via MyD88 Signaling to Control Listeria monocytogenes Infection
Researchers showed that myeloid differentiation factor 88 (MyD88) signaling in dendritic cells is sufficient to mediate the protective innate response, including the production of proinflammatory cytokines, neutrophil infiltration, bacterial clearance, and full protection from lethal infection. [Cell Rep]
Full Article | Graphical Abstract

HIV

Human Protein Staufen-2 Promotes HIV-1 Proliferation by Positively Regulating RNA Export Activity of Viral Protein Rev
Researchers established that human Staufen-2, a host factor which is up-regulated upon HIV-1 infection, interacts with HIV-1 Rev, thereby promoting its RNA export activity and progeny virus formation. [Retrovirology] Abstract | Full Article

HIV-2 Vpx Interacts with IRF5 and Inhibits Its Function
Researchers demonstrated that HIV-2 Vpx interacts with interferon regulatory factor (IRF)5, and Vpx inhibits IRF5-mediated transactivation. Expression of Vpx in THP-1 cells reduced mRNA levels and protein production of Toll-like receptor dependent IL6, IL12p40 and TNFa induced by lipopolysaccharide, R848 and ODN2216. [J Biol Chem] Abstract | Full Article

Differential Blood and Mucosal Immune Responses against an HIV-1 Vaccine Administered via Inguinal or Deltoid Injection
Researchers performed a randomized, double-blinded, placebo-controlled Phase I trial in HIV-1-uninfected volunteers, using the recombinant Canarypox vaccine vCP205 delivered by different routes. HIV-1-specific CD8⁺ T lymphocytes were observed in 7/12 vaccinees, and blood and gut targeting were distinct. [PLoS One]
Full Article

Toll-Like Receptor 3 Signaling Up-Regulates Expression of the HIV Co-Receptor G-Protein Coupled Receptor 15 on Human CD4⁺ T Cells
Scientists showed that GPR15 expression in CD4⁺ T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. [PLoS One] Full Article

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Innate Resistance against Toxoplasma gondii: An Evolutionary Tale of Mice, Cats, and Men
Recent studies have revealed remarkable species specificity of the Toll-like receptors (TLRs) TLR11 and TLR12 and the immunity-related GTPase proteins that are essential elements for detection and immune control of Toxoplasma gondii in mice, but not in humans. The biological and evolutionary implications of these findings for the T. gondii host-pathogen relationship and for human disease are discussed. [Cell Host Microbe] Abstract

A Neglected Epidemic: Fungal Infections in HIV/AIDS
The authors summarize the current state of the-art in AIDS-related mycoses, and the key action points required to improve outcomes from these devastating infections. [Trends Microbiol] Abstract

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Phase I Clinical Trial Begins for Malaria Vaccine Candidate Based on iBio’s Proprietary Technology
iBio, Inc. reported the initiation of a Phase I human safety and immunogenicity clinical study of a transmission-blocking malaria vaccine candidate. [iBio, Inc.] Press Release

CytoDyn Submits Protocol to FDA for Phase IIb Clinical Study of PRO 140 for Treatment Substitution in Patients with HIV
CytoDyn Inc. announced that the company has submitted a Phase IIb clinical trial protocol, for its lead product candidate, PRO 140, to the U.S. Food and Drug Administration (FDA) for treatment substitution in patients with HIV. PRO 140 is a humanized monoclonal antibody directed against CCR5, a molecular portal that HIV uses to enter cells, and belongs to a class of HIV therapies known as entry inhibitors that block HIV from entering into and infecting certain cells. [CytoDyn Inc.] Press Release

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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 Faculty Position – Vaccine Immunology (Cornell University)

NEW Postdoctoral Research Scientist – HIV (French Agency for Research on HIV and Viral Hepatitis)

NEW Research Technologist – Pluripotent Stem Cells (STEMCELL Technologies Inc.)

NEW Research Technologist – Particle Chemistry (STEMCELL Technologies Inc.)

NEW Research Technologist – PSC Biology and Bioengineering (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (Institut für Klinische Chemie und Pathobiochemie Klinikum rechts der Isar)

Assistant Professor – Viral Oncologist (University of Maryland School of Medicine)

Postdoctoral Scientist – Avian Viral Diseases (The Pirbright Institute)

Postdoctoral Position – Epigenetic Regulation of Interleukin-12 Family Members (Université Libre de Bruxelles)

Research Associate – Translational Immunology (Genentech, Inc.)

Associate Professor – B Cell Immunologist (Institute of Human Virology at the University of Maryland School of Medicine)

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