Strategic Choices and Changes in the International Political Economy

Europe 1992 has become a major focus of attention for the Western media, because if all goes as planned, a unified and integrated common market of 12 nations and 320 million consumers will be created, a market running from the mountains of Mourne to the Peloponnese with a GNP rivaling that of the United States. Further east, the Kremlin is determined to put the Soviet Union\u27s tattered economic house in order under Gorbachev’s much ballyhooed perestroika strategy. And along Asia\u27s Pacific rim, rapid growth may permit this region to match the productive capacity of both the United States and the European Community within the next two decades

The Role of Subnational Governments in Sectoral Integration

subnational governments and sectoral integratio

The Role of State and Provincial Governments in Canada-U.S. Sectoral Integration

state and provincial governments and sectoral integratio

The Membrane Fusion Step of Vaccinia Virus Entry Is Cooperatively Mediated by Multiple Viral Proteins and Host Cell Components

For many viruses, one or two proteins allow cell attachment and entry, which occurs through the plasma membrane or following endocytosis at low pH. In contrast, vaccinia virus (VACV) enters cells by both neutral and low pH routes; four proteins mediate cell attachment and twelve that are associated in a membrane complex and conserved in all poxviruses are dedicated to entry. The aim of the present study was to determine the roles of cellular and viral proteins in initial stages of entry, specifically fusion of the membranes of the mature virion and cell. For analysis of the role of cellular components, we used well characterized inhibitors and measured binding of a recombinant VACV virion containing Gaussia luciferase fused to a core protein; viral and cellular membrane lipid mixing with a self-quenching fluorescent probe in the virion membrane; and core entry with a recombinant VACV expressing firefly luciferase and electron microscopy. We determined that inhibitors of tyrosine protein kinases, dynamin GTPase and actin dynamics had little effect on binding of virions to cells but impaired membrane fusion, whereas partial cholesterol depletion and inhibitors of endosomal acidification and membrane blebbing had a severe effect at the later stage of core entry. To determine the role of viral proteins, virions lacking individual membrane components were purified from cells infected with members of a panel of ten conditional-lethal inducible mutants. Each of the entry protein-deficient virions had severely reduced infectivity and except for A28, L1 and L5 greatly impaired membrane fusion. In addition, a potent neutralizing L1 monoclonal antibody blocked entry at a post-membrane lipid-mixing step. Taken together, these results suggested a 2-step entry model and implicated an unprecedented number of viral proteins and cellular components involved in signaling and actin rearrangement for initiation of virus-cell membrane fusion during poxvirus entry