Immunology of Infectious Disease News Volume 1.37 | Nov 27 2013

Subinfectious Hepatitis C Virus Exposures Suppress T Cell Responses against Subsequent Acute Infection
Investigators showed in nonhuman primates that repeated exposure to human plasma with trace amounts of Hepatitis C virus (HCV) induced HCV-specific T cells without seroconversion and systemic viremia but did not protect upon subsequent HCV challenge. [Nat Med] Abstract

Langerhans Cells Are Generated by Two Distinct PU.1-Dependent Transcriptional Networks
Scientists addressed the function of a group of key dendritic cell transcription factors-PU.1, ID2, IRF4, and IRF8-in the establishment of the Langerhans cell (LC) network. They showed that although steady-state LC homeostasis depends on PU.1 and ID2, the latter is dispensable for bone marrow-derived LCs. PU.1 controls LC differentiation by regulating the expression of the critical TGF-β responsive transcription factor RUNX3. [J Exp Med] Abstract

The Impact of Hepatitis B Virus Precore/Core Gene Carboxyl Terminal Mutations on Viral Biosynthesis and the Host Immune Response
The authors analyzed the hepatitis B virus (HBV) precore/core gene sequences by cloning method in 33 chronic HBV-infected patients during the inflammatory phase before spontaneous HBeAg-seroconversion. The impact of the most prevalent mutant on HBeAg biosynthesis was assessed by Western blot and native agarose gel analysis in Huh7 cells, and the human immune responses were assessed by in vitro stimulation of CD3+CD8+ T lymphocytes of chronic HBV-infected subjects. [J Infect Dis] Abstract

Analysis of Localized Immune Responses Reveals Presence of Th17 and Treg Cells in Cutaneous Leishmaniasis due to Leishmania tropica
Researchers employed cytokine/chemokine/receptor membrane cDNA array to capture comprehensive picture of immuno-determinants in localized human tissue during L. tropica infection. Expression of selected molecules was evaluated by real time PCR in dermal lesion tissues at pre- and post-treatment stages. Plasma IL-17 level was estimated by sandwich ELISA. [BMC Immunol] Full Article

HIV

The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral cDNA by the Innate Sensor cGAS in Dendritic Cells
Capsid-mutated HIV-2 revealed that sensing by the host requires viral cDNA synthesis, but not nuclear entry or genome integration. The HIV-1 capsid prevented viral cDNA sensing up to integration, allowing the virus to escape innate recognition. In contrast, dendritic cells sensed capsid-mutated HIV-1 and enhanced stimulation of T cells in the absence of productive infection. [Immunity] Abstract | Graphical Abstract | Press Release

Site-Specific Genome Editing in PBMCs with PLGA Nanoparticle-Delivered PNAs Confers HIV-1 Resistance in Humanized Mice
Investigators demonstrated the feasibility of poly (lactic-co-glycolic acid)(PLGA)-nanoparticle-encapsulated peptide nucleic acidN (PNAs)-based gene-editing molecules for the targeted modification of CCR5 in human human peripheral blood mononuclear cells (PBMCs) as a platform for conferring HIV-1 resistance. [Mol Ther] Full Article

HIV-1 Infection of Macrophages Dysregulates Innate Immune Responses to Mycobacterium tuberculosis by Inhibition of Interleukin 10
Researchers tested the hypothesis that HIV-1 may modulate macrophage responses to co-infection with Mycobacterium tuberculosis (Mtb). HIV-1 caused exaggerated pro-inflammatory responses to Mtb that supported enhanced virus replication, and were associated with deficient stimulus-specific induction of anti-inflammatory interleukin 10 and attenuation of mitogen activated kinase signalling downstream of TLR2 and dectin-1 stimulation. [J Infect Dis] Abstract

Inhibition of R5-Tropic Human Immunodeficiency Virus Type-1 Replication in CD4⁺ Natural Killer T Cells by Gamma-Delta T Lymphocytes
The authors confirmed that CD4⁺ natural killer T (NKT) cells derived from peripheral blood mononuclear cells (PBMCs) predominantly express CCR5 rather than CXCR4, while the reverse is true for CD4⁺ T cells derived from circulating PBMCs, and that R5-tropic HIV-1 expands efficiently in the CD4⁺ NKT cells. [Immunology] Abstract

Immune Quiescence: A Model of Protection against HIV Infection
The authors present evidence from studies of HIV transmission in the context of clinical trials and HIV-exposed seronegative cohorts that implicates elevated immune activation as a risk factor for acquiring HIV. [Retrovirology] Full Article

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British Scientists to Trial Potential HIV Cure
Scientists and clinicians from five leading UK universities will begin a groundbreaking trial next year to test a possible cure for HIV infection. Fifty patients in the early stages of HIV infection will take part in the trial. [Imperial College London] Press Release

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NEW Research Fellow – Influence of the Lung Microbiome on Host Immune Response to Respiratory Pathogens (Queen’s University Belfast)

Postdoctoral Fellowship – Anti-Viral Property of IL-27 and Related Proteins in Innate Immune Responses to HIV and Other Virus Infections (Leidos Biomedical Research, Inc.)

Postdoctoral Position – Pathogenesis of Enterovirus 71 (Institut Pasteur)

Postdoctoral Position – Importance of Trypanosome Motility during the Early Infection in the Mammalian Host (Institut Pasteur)

PhD Studentship – Systems Biology (University of Oxford)

PhD Studentship – HIV Transcriptional Latency and Activation (Erasmus MC)

Junior and Senior Research Scientists – Novel, Small Molecule HIV Drug Discovery (Sirga Advanced Biopharma, Inc.)

Tenure-Track Faculty Position – Women’s Infectious Disease Research (Washington University School of Medicine)

Residency in Infectious Diseases (University of Florida)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

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