Ebolavirus Is Internalized into Host Cells via Macropinocytosis in a Viral Glycoprotein-Dependent Manner

Ebolavirus (EBOV) is an enveloped, single-stranded, negative-sense RNA virus that causes severe hemorrhagic fever with mortality rates of up to 90% in humans and nonhuman primates. Previous studies suggest roles for clathrin- or caveolae-mediated endocytosis in EBOV entry; however, ebolavirus virions are long, filamentous particles that are larger than the plasma membrane invaginations that characterize clathrin- or caveolae-mediated endocytosis. The mechanism of EBOV entry remains, therefore, poorly understood. To better understand Ebolavirus entry, we carried out internalization studies with fluorescently labeled, biologically contained Ebolavirus and Ebolavirus-like particles (Ebola VLPs), both of which resemble authentic Ebolavirus in their morphology. We examined the mechanism of Ebolavirus internalization by real-time analysis of these fluorescently labeled Ebolavirus particles and found that their internalization was independent of clathrin- or caveolae-mediated endocytosis, but that they co-localized with sorting nexin (SNX) 5, a marker of macropinocytosis-specific endosomes (macropinosomes). Moreover, the internalization of Ebolavirus virions accelerated the uptake of a macropinocytosis-specific cargo, was associated with plasma membrane ruffling, and was dependent on cellular GTPases and kinases involved in macropinocytosis. A pseudotyped vesicular stomatitis virus possessing the Ebolavirus glycoprotein (GP) also co-localized with SNX5 and its internalization and infectivity were affected by macropinocytosis inhibitors. Taken together, our data suggest that Ebolavirus is internalized into cells by stimulating macropinocytosis in a GP-dependent manner. These findings provide new insights into the lifecycle of Ebolavirus and may aid in the development of therapeutics for Ebolavirus infection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

ネツ ショック ゼンショチ ニ ヨル カン キョケツ サイカンリュウ ショウガイジ ノ TNF アルファ サンセイ オヨビ コウチュウキュウ シンジュン ノ ヨクセイ コウカ ニ カンスル ケンキュウ

京都大学0048新制・課程博士博士(医学)甲第9424号医博第2437号新制||医||789(附属図書館)UT51-2002-G182京都大学大学院医学研究科外科系専攻(主査)教授 田中 紘一, 教授 千葉 勉, 教授 山岡 義生学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Alternate stacking of transition metal ions and terephthalic acid molecules for the fabrication of self-assembled multilayers

Self-assembled multilayers consisting of transition metal ions and biscarboxyl acid molecules have been fabricated by a layer-by-layer chemisorption technique. As transition metal ion, zirconium (Zr(IV)) or titanium (Ti(IV)) was employed, while terephthalic acid (TPA) was used as biscarboxyl molecule. In the multilayers, two TPA monolayers were bridged by one monolayer of Zr(IV) or Ti(IV) most likely through coordination bonds between the metal ions and the carboxyl groups in the TPA molecules. Although the both transition metal ions were successfully applied to construct multilayers, the multilayer structure of the Ti–TPA system was more disordered than that of the Zr–TPA system as revealed by grazing incidence X-ray reflectivity