JCI online early table of contents: Sept. 8, 2009
EDITOR'S PICK: Engineered human fusion protein protects against HIV-1 infection
In 2004, Jeremy Luban and colleagues from the University of Geneva, Switzerland, reported that New World owl monkeys (Aotus genus) make a fusion protein - AoT5Cyp - that potently blocks HIV-1 infection. The human genome encodes the equivalent of the 2 components of AoT5Cyp (i.e., TRIM5 and cyclophilin A), but humans unfortunately do not make the T5Cyp fusion protein. In their new study in the Journal of Clinical Investigation, Luban et al. have engineered a human HIV-1 inhibitor modeled after AoT5Cyp, by fusing human cyclophilin A to human TRIM5 (hT5Cyp). The human fusion protein blocked HIV-1 infection of human macrophage and T cell lines, without disrupting normal cell function. Mice engineered to lack B, T, and NK immune cells (to ensure that the animals do not reject grafts of human material) were then engrafted with human CD4+ T cells engineered to contain hT5Cyp. HIV-1 replication was potently inhibited in these animals. The authors concluded that hT5Cyp is a robust inhibitor of HIV-1 replication and a promising anti-HIV-1 gene therapy candidate.
TITLE: Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components
AUTHOR CONTACT:
Jeremy Luban
University of Geneva, Geneva, Switzerland.
Phone: 41-22-379-5720; Fax: 41-22-379-5702; E-mail: jeremy.luban@unige.ch
View the PDF of this article at: https://www.the-jci.org/article.php?id=39354
ONCOLOGY: TNF-alpha promotes ovarian tumors with a little help from friends TNFR1 and IL-17
TITLE: The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans
AUTHOR CONTACT:
Thorsten Hagemann
Queen Mary University of London, London, United Kingdom.
Phone: 44-20-78825795; Fax: 44-20-78826110; E-mail: t.hagemann@qmul.ac.uk
View the PDF of this article at: https://www.the-jci.org/article.php?id=39065
CARDIOLOGY: Cdc42 restrains hypertrophy in the heart
TITLE: Cdc42 is an antihypertrophic molecular switch in the mouse heart
AUTHOR CONTACT:
Jeffery D. Molkentin
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Phone: (513) 636-3557; Fax: (513) 636-5958; E-mail: jeff.molkentin@cchmc.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=37694
CELL BIOLOGY: Kinase CAMKII links multiple mechanisms of stress-induced cell death
TITLE: Calcium/calmodulin-dependent protein kinase II links ER stress with Fas and mitochondrial apoptosis pathways.
AUTHOR CONTACT:
Ira Tabas
Columbia University, New York, New York, USA.
Phone: (212) 305-9430; Fax: (212) 305-4834; E-mail: iat1@columbia.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=38857
Source: Journal of Clinical Investigation
