Immunology of Infectious Disease News Volume 4.05 | Feb 10 2016

NFAT Transcription Factors Promote the Generation of Follicular Helper T Cells in Response to Acute Viral Infection
The authors showed that deficiency in NFAT1 and NFAT2 in CD4⁺ T cells leads to impaired germinal center reactions upon viral infection because of reduced follicular CD4⁺ Th cell differentiation and defective expression of proteins involved in T/B interactions and B cell help, including ICOS, PD-1, and SLAM family receptors. [J Immunol] Abstract

Control of Influenza Infection Is Impaired by Diminished Interferon-γ Secretion by CD4 T Cell in the Lungs of Toddlers
Researchers hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. They developed a young mouse model to examine potential divergent responses between toddlers and adults. [J Leukoc Biol] Abstract

Cross-Specific T-Cell Responses in Acute Hepatitis E Virus (HEV) Infection
Scientists investigated HEV-specific T-cell responses using genotypes 3- and 1-specific overlapping peptides. Broad functional HEV-specific CD4⁺ and CD8⁺ T-cell responses were detectable in patients acutely infected with HEV genotype 3. [J Viral Hepat] Abstract

HIV

ART Influences HIV Persistence in the Female Reproductive Tract and Cervicovaginal Secretions
Scientists implemented an in vivo model of antiretroviral therapy (ART) in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. They demonstrated that the entire female reproductive tract of BLT mice is reconstituted with human CD4⁺ cells that are shed into cervicovaginal secretions. [J Clin Invest] Full Article | Press Release

Dasatinib Inhibits HIV-1 Replication through the Interference of SAMHD1 Phosphorylation in CD4⁺ T Cells
Researchers demonstrated that Dasatinib can actually interfere with SAMHD1 phosphorylation in human peripheral blood lymphocytes, preserving its antiviral activity against HIV-1. Dasatinib prevented SAMHD1 phosphorylation in vitro and ex vivo, impairing HIV-1 reverse transcription and proviral integration. [Biochem Pharmacol] Abstract

Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size
Investigators showed that central memory CD4 T cells (TCM) from HIV infected individuals have heightened expression of BCL-2 relative to procaspase 8, possibly explaining the persistence of HIV-infected TCM despite generation of Casp8p41. [J Virol] Abstract

Expansion of Inefficient HIV-Specific CD8⁺ T Cells during Acute Infection
Studying individuals in the first few days of acute HIV infection, the authors detected the emergence of a unique population of CD38⁺CD27^–CD8⁺ T cells characterized by a low expression of the CD8 receptor. [J Virol] Abstract

Brain Invasion by CD4⁺ T Cells Infected with a Transmitted/Founder HIV-1_BJZS7 during Acute Stage in Humanized Mice
By measuring viral load, P24 antigenemia and P24⁺ cells in peripheral blood and various tissue compartments, investigators found that systemic infections were rapidly established in NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice reconstituted with human PBMC by both HIV-1 strains. [J Neuroimmune Pharmacol] Abstract

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Recent Developments in the Effort to Cure HIV Infection: Going beyond N = 1
Investigators detail progress in the understanding of the molecular and cellular mechanisms of viral latency, efforts to accurately assess the size and composition of the latent reservoir, the characterization and development of HIV-targeted broadly neutralizing antibodies and cytolytic T lymphocytes, and animal models for the study HIV latency and therapeutic strategies. [J Clin Invest] Abstract

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Vilcek Foundation Honors Prominent Immunologist and Young Researchers of Promise
The Vilcek Foundation announced immunologist Dan R. Littman as the winner of the 2016 Vilcek Prize in Biomedical Science. His work helped unravel HIV pathogenesis and paved the way for therapeutic approaches to HIV and inflammatory and autoimmune diseases. [Vilcek Foundation] Press Release

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NEW Administrative Head – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Senior Scientist – Immunology (Bavarian Nordic GmbH)

Global Medical Leader – Infectious Diseases (F. Hoffmann-La Roche)

Research Associate – Bacterial Infection in the Context of Antimicrobial Resistance (Imperial College London)

Postdoctoral Position – Immunological Impact of Endogenous Retroviruses (The Francis Crick Institute)

Postdoctoral Position – Immunology (Indiana University School of Medicine)

Postdoctoral Position – Hantavirus and Inflammation Research (Karolinska Institutet)

Research Technician I – HIV Vaccine Trials (Fred Hutchinson Cancer Research Center)

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