Immunology of Infectious Disease News Volume 5.25 | Jun 28 2017

TOP STORY

Nlrp9b Inflammasome Restricts Rotavirus Infection in Intestinal Epithelial Cells

Rotavirus infects intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signaling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. Investigators uncovered and mechanistically characterized the NOD-like receptor Nlrp9b that is specifically expressed in intestinal epithelial cells and restricts rotavirus infection. [Nature] Abstract | Press Release

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VP4- and VP7-Specific Antibodies Mediate Heterotypic Immunity to Rotavirus in Humans

Scientists used rotavirus (RV)-specific single cell–sorted intestinal B cells from human adults, barcode-based deep sequencing of antibody repertoires, monoclonal antibody expression, and serologic and functional characterization to demonstrate that infection-induced heterotypic immunoglobulins primarily directed to VP5*, the stalk region of the RV attachment protein, VP4, were able to mediate heterotypic protective immunity. [Sci Transl Med] Abstract

HTLV-1-Induced Leukotriene B4 Secretion by T Cells Promotes T Cell Recruitment and Virus Propagation

The authors demonstrated that human T-lymphotropic virus type 1-infected CD4 T cells secrete a potent chemoattractant, leukotriene B4 (LTB4). LTB4 secretion was dependent on Tax-induced transactivation of the pla2g4c gene, which encodes the cytosolic phospholipase A2 gamma. Inhibition of LTB4 secretion or LTB4 receptor knockdown on target cells reduces T-cell recruitment, cellular contact formation and virus propagation in vitro. [Nat Commun] Full Article

The Human Cytomegalovirus Glycoprotein pUL11 Acts via CD45 to Induce T Cell IL-10 Secretion

Researchers showed that treatment of peripheral blood mononuclear cells with purified pUL11 induces IL-10 producing T cells as a result of pUL11 binding to the CD45 phosphatase on T cells. IL-10 production induced by human cytomegalovirus infection was also in part mediated by pUL11. [PLoS Pathog] Full Article

Dengue Virus Evades AAV-Mediated Neutralizing Antibody Prophylaxis in Rhesus Monkeys

Investigators used recombinant adeno-associated viruses (rAAV) to deliver the anti-dengue virus 3 (DENV3) neutralizing antibody P3D05. While the administration of rAAV-P3D05-rhIgG1-L234A-L235A to Rhesus macaques engendered DENV3-neutralizing activity in serum, it did not prevent infection. [Mol Ther] Abstract

Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology

The authors describe an innovative vaccinia virus-derived vaccine platform technology termed ‘Sementis Copenhagen Vector’, which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene, D13L. [Mol Ther] Full Article | Graphical Abstract

HIV

Combined Single-Cell Quantitation of Host and SIV Genes and Proteins Ex Vivo Reveals Host-Pathogen Interactions in Individual Cells

Scientists integrated two single-cell technologies, flow cytometry and highly multiplexed quantitative RT-PCR, to characterize SIV-infected CD4 T cells directly ex vivo. Within individual cells, they correlated the cellular phenotype, in terms of host protein and RNA expression, with stages of the viral life cycle defined by combinatorial expression of viral RNAs. [PLoS Pathog] Full Article

Impaired Downregulation of NKG2D Ligands by Nef Protein from Elite Controllers Sensitizes HIV-1-Infected Cells to ADCC

Since HIV-1 Nef has been reported to reduce the expression of NKG2D ligands, investigators evaluated the relative abilities of Nef from elite controllers (ECs) and progressors to downmodulate NKG2D ligands. Furthermore, they assessed the impact of ECs and progressor Nef on the antibody-dependent cellular cytotoxicity (ADCC) susceptibility of HIV-1-infected cells. [J Virol] Abstract

Potent Inhibition of HIV-1 Replication in Resting CD4 T Cells by Resveratrol and Pterostilbene

Researchers demonstrated that resveratrol and pterostilbene completely block HIV-1 infection at low micromolar dose in resting CD4 T cells, primarily at the reverse transcription step. The anti-HIV effect was fully reversed by exogenous deoxynucleosides and Vpx, a simian immunodeficiency virus protein that increases dNTP levels. [Antimicrob Agents Chemother] Abstract

HIV-Tat Regulates Macrophage Gene Expression in the Context of neuroAIDS

Using THP-1 cells, a human monocyte/macrophage cell line, and their infection with lentivirus, scientists generated stable cell lines that express Tat-Flag. They performed ChIP-seq analysis of these cells and found 66 association sites of Tat in promoter or coding regions. Among these are C5, CRLF2/TSLPR, BDNF, and APBA1/Mint1, genes associated with inflammation/damage. [PLoS One] Full Article

The Association between Detected Drug Resistance Mutations and CD4⁺ T-Cell Decline in HIV-Positive Individuals Maintained on a Failing Treatment Regimen

Researchers sought to analyze the effect of drug resistance mutations (DRMs) on CD4 cell trends in HIV-positive people maintained on virologically failing antiretroviral therapy. After adjustment, CD4 counts declined less steeply during episodes where DRMs were detected compared to episodes with no DRMs. [Antivir Ther] Abstract

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The Phenotype and Function of Preterm Infant Monocytes: Implications for Susceptibility to Infection

The authors present an integrated view of human studies focused on monocyte functions in preterm infants. They discuss how a developmental immaturity of these cells may contribute to preterm infants’ susceptibility to infections. [J Leukoc Biol] Abstract

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Smithers Poster Confirms Guinea Pig Model for Preclinical Vaccine Safety Testing

Smithers Avanza announced that Senior Toxicologist Caitlin Murphy, PhD presented a poster titled, “Evaluation of Maternal Transplacental Transfer of Anti-F-Antibodies to Pups Following Immunization of Pregnant Hartley Guinea Pigs with a Recombinant Respiratory Syncytial Virus Vaccine”. [Press release from Smithers Avanza discussing research presented at the 57^th Annual Meeting of the Teratology Society, Denver] Press Release

NanoViricides’ Poster “Novel Nanoviricides^® Highly Effective against Varicella Zoster Virus in Cell Culture” Presented

NanoViricides, Inc. announced that its poster entitled “Novel Nanoviricides^® Highly Effective Against Varicella Zoster Virus in Cell Culture” was presented. [Press release from NanoViricides, Inc. (PR Newswire Association LLC.) discussing research presented at the 36^th Annual Meeting of the American Society of Virology (ASV), Madison] Press Release

Roche Receives FDA Approval for Fourth-Generation HIV Combination Antigen-Antibody Assay — Allowing Detection of Infection with High Sensitivity and Specificity

Roche announced that its fourth-generation HIV combination antigen-antibody assay, the Elecsys HIV combi PT assay, has received U.S. Food and Drug Administration (FDA) PMA approval. [Roche (PR Newswire Association LLC.)] Press Release

China Donates Equipment to Help Zika Fight in Guyana

Public Health Minister Volda Lawrence accepted G$20M in medical equipment and supplies from the Government of China to help in the fight against Zika and other infectious diseases. [Department of Public Information, Guyana] Press Release

Vaccine Ruling from Europe’s Highest Court Isn’t as Crazy as Scientists Think

The Court of Justice of the European Union (EU) in Luxembourg handed down a judgment in a compensation case involving a French man who claimed that a vaccination for hepatitis B caused his multiple sclerosis. The ruling specifies what type of evidence is allowed in EU member states in such cases, but it prompted a flurry of negative press coverage. [Nature News] Editorial

Putin Tightens Control over Russian Academy of Sciences

The Russian government has taken further steps to tighten its grip on the Russian Academy of Sciences (RAS) in Moscow. The State Duma—one of the two chambers of the Russian parliament—passed the first draft of a new law that would give president Vladimir Putin the final say in the elections for RAS’s presidency. [ScienceInsider] Editorial

NEW 3^rd Global Summit on Virology
August 21-23, 2017
Barcelona, Spain

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NEW Postdoctoral Research Assistant – Immunology of Infectious Diseases (University of Oxford)

Postdoctoral Researcher – Orbivirus (The Pirbright Institute)

Postdoctoral Position – Infectious Diseases Pathogenesis (Massachusetts General Hospital & Harvard Medical School)

Research Associate – HIV Immunology (University College London)

Postdoctoral Scientist – HIV-1 and Malaria Vaccine Research (Center for Infectious Disease Research)

Postdoctoral Position – HIV in T Cells (Ludwig-Maximilians-Universität München)

Scientist – Immunology, Infectious Diseases (Regeneron)

Physician Scientist – Molecular Basis of Microbial Pathogenesis (Virginia Commonwealth University)

Research Scientist – Microbiology/Molecular Biology (Day Zero Diagnostics)

Lab Aide – Infectious Disease Sciences Program (Fred Hutchinson Cancer Research Center)

Cell Biology Scientists – T Cells Responsive to Various Infectious Disease Targets (Immunocore)

Scientist I/II – Analytical Development (KBI Biopharma)

Staff Clinician Position – Laboratory of Clinical Infectious Diseases (National Institute of Allergy and Infectious Diseases)

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