(Press-News.org) Double-stapled peptide inhibits RSV infection
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, generating life-threating illness in very young and elderly populations. Despite great effort, preventive therapies are limited. RSV enters host cells through the fusion protein RSV F, which forms a six-helix fusogenic bundle. Small interfering peptides that prevent bundle formation limit RSV infection in vitro; however, these peptides are highly susceptible to degradation. In this issue of the Journal of Clinical Investigation, Loren Walensky and colleagues at the Dana-Farber Cancer Institute applied hydrocarbon stapling to stabilize the α-helical structure of an RSV F peptide (SAH-RSV). Pretreatment with SAH-RSV prevented infection in both cell culture and murine models of RSV. Intranasal delivery prevented viral infection within the nares, while intratracheal delivery of a nanoparticle preparation of SAH-RSV prevented RSV infection in the lung. In the companion Commentary, Sarah Katen and Terrence Dermody of Vanderbilt University discuss the implications of this study for RSV prevention.
TITLE:
Mucosal delivery of a double-stapled RSV peptide prevents nasopulmonary infection
AUTHOR CONTACT:
Loren Walensky
Dana-Farber Cancer Institute, Boston, MA, USA
Phone: 617-632-6307; Fax: 617-582-8240; E-mail: loren_walensky@dfci.harvard.edu
View this article at: http://www.jci.org/articles/view/71856
ACCOMPANYING COMMENTARY
TITLE:
Repurposing staples for viruses: applying peptide design to RSV prophylaxis
AUTHOR CONTACT:
Terence S. Dermody
Vanderbilt University School of Medicine, Nashville, TN, USA
Phone: 615-343-9943; Fax: 615-343-9723; E-mail: terry.dermody@vanderbilt.edu
View this article at: http://www.jci.org/articles/view/75797
Fibroblast-derived exosomes mediate caridiomyocyte hypertrophy via microRNA delivery
Cardiovascular disease promotes a progressive, pathological heart remodeling that is characterized by fibrosis, and cardiomyocyte hypertrophy. Gene expression patterns associated with heart disease are linked alterations in microRNAs (miRNAs), which in addition to regulating intracellular target gene expression can affect gene expression in neighboring cells. In this issue of the Journal of Clinical Investigation, Thomas Thum and colleagues at Hanover Medical School provide evindence that cardiac fibroblasts release miRNA-enriched that are taken up by neighboring cardiomyocytes and promote hypertrophy. Surprisingly, many of the miRNAs enriched in fibroblast-derived exosomes were miRNA passenger strands (miRNA*), which are typically degraded in the cytoplasm. In particular, miR-21* was required for altering cardiomyocyte-associated protein profiles, and pharmacological inhibition of miR-21* reduced angiotensin II-induced cardiac hypertrophy in a murine model. In the accompanying Commentary, Ciro Indolfi of Magna Graecia University discusses the clinical implications of targeting exosome-mediated communication between cardiac fibroblasts and myocytes.
TITLE:
Cardiac fibroblast–derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy
AUTHOR CONTACT:
Thomas Thum
Hannover Medical School, Hannover, DEU
Phone: +495115325272; Fax: +495115325274; E-mail: thum.thomas@mh-hannover.de
View this article at: http://www.jci.org/articles/view/70577
ACCOMPANYING COMMENTARY
TITLE:
Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy
AUTHOR CONTACT:
Ciro Indolfi
Magna Graecia University, Catanzaro, , ITA
Phone: +3909613697067; E-mail: indolfi@unicz.it
View this article at: http://www.jci.org/articles/view/75801
Patient response to cryptococcosis is dependent on fungal-specific factors
Cryptococcal meningitis is a serious secondary complication of HIV infection that results in substantial patient mortality. Patient fungal burden in the cerebrospinal fluid (CSF) at time of diagnosis and response to antifungal therapy are predictive of disease outcome; however, cryptococcal-specific phenotypes have not been associated with clinical presentation. In this issue of the Journal of Clinical Investigation, Robin May and colleagues at the University of Birmingham evaluated 65 clinical Cryptococcus neoformans isolates collected from HIV+ individuals enrolled in clinical trials to evaluate the strain-specific impact on long-term patient survival. C. neoformans isolates that exhibited enhanced uptake by macrophages in vitro and increased laccase activity were associated with increased fungal burden, response to antifungal treatment, and increased patient mortality. In a companion Commentary, John Perfect of Duke University notes that understanding both pathogen and host-specific factors in disease etiology will enhance therapeutic strategies for treating cryptococcosis.
TITLE:
Efficient phagocytosis and laccase activity affect the outcome of HIV-associated cryptococcosis
AUTHOR CONTACT:
Robin C. May
University of Birmingham, Birmingham, United Kingdom
Phone 44.0.121.4145418; Fax: 44.0.1214145925; E-mail: r.c.may@bham.ac.uk
View this article at: http://www.jci.org/articles/view/72950
ACCOMPANYING COMMENTARY
TITLE:
Cryptococcosis: a model for the understanding of infectious diseases
AUTHOR CONTACT:
John Perfect
Duke University, Durham, NC, USA
Phone: 919 684 4016; Fax: 919 684 8902; E-mail: perfe001@mc.duke.edu
View this article at: http://www.jci.org/articles/view/75241
The coinhibitory receptor PD-1H suppresses T cell responses
The balance between coinhibitory and costimulatory molecules on antigen presenting cells (APCs) are crucial for proper regulation of T cell responses and inflammation. Programmed death 1 homologue (PD-1H) on APCs suppresses T cell responses, and agonist and blocking antibodies targeting this ligand have been shown to exacerbate and ameliorate inflammatory conditions, respectively. In this issue of the Journal of Clinical Investigation, Leiping Chen and colleagues at Yale University examined the T cell responses in mice lacking PD-1H and found that these animals exhibit an enhanced immune response to antigen stimulation. Compared to controls animals lacking PD-1H were resistant to tumor induction in a transplant model of brain glioma. This resistance required the presence of CD4+ T cells. Administration of an agonist PD-1H antibody to mice with experimental acute hepatitis reduced disease through suppression of CD4+ T cells. In an accompanying Commentary, Yang Liu of Children's National Medical Center remarks that this study provides further evidence that targeting PD-1H has potential for treating inflammatory disease and cancers.
TITLE:
Coinhibitory receptor PD-1H preferentially suppresses CD4+ T cell–mediated immunity
AUTHOR CONTACT:
Lieping Chen
Yale University School of Medicine, New Haven, CT, USA
Phone: 203-737-1819; E-mail: lieping.chen@yale.edu
MEDIA REATIONS CONTACT
Vicky Agnew
Yale Cancer Center, New Haven, CT, USA
Phone: 203-785-7001; Email: vicky.agnew@yale.edu
View this article at: http://www.jci.org/articles/view/74589
ACCOMPANYING COMMENTARY
TITLE:
A VISTA on PD-1H
AUTHOR CONTACT:
Yang Liu
Children's National Medical Center, Washington, D.C., DC, USA
Phone: 202-476-5849; E-mail: yaliu@cnmc.org
View this article at: http://www.jci.org/articles/view/75798
ALSO IN THIS ISSUE:
TITLE:
Type-1 angiotensin receptors on macrophages ameliorate IL-1 receptor-mediated kidney fibrosis
AUTHOR CONTACT:
Steven Crowley
Duke University Medical Center, Durham, NC, USA
Phone: 919-684-9788; E-mail: steven.d.crowley@duke.edu
View this article at: http://www.jci.org/articles/view/61368
TITLE:
Monocytes expressing CX3CR1 orchestrate the development of vincristine-induced pain
AUTHOR CONTACT:
Marzia Malcangio
King's College London, London, GBR
Phone: 004420-7848 6092; E-mail: marzia.malcangio@kcl.ac.uk
View this article at: http://www.jci.org/articles/view/71389
TITLE:
Multifactorial ERβ and NOTCH1 control of squamous differentiation and cancer
AUTHOR CONTACT:
Gian Paolo Dotto
University of Lausanne, Epalinges, CHE
Phone: +41/21 692 57 20; Fax: +41/21 692 57 05; E-mail: gian-paolo.dotto@unil.ch
View this article at: http://www.jci.org/articles/view/72718
TITLE:
Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart
AUTHOR CONTACT:
Fatima Smih
INSERMU1048, Toulouse, FRA
Phone: 33 685 561 529; E-mail: fatima.smith-rouet@inserm.fr
View this article at: http://www.jci.org/articles/view/74668
INFORMATION:
JCI online ahead of print table of contents for April 17, 2014
2014-04-18
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