The Paradoxes of Paramountcy: Regional Rivalries and the Dynamics of American Hegemony in East Asia

It has become increasingly commonplace to describe the United States as hegemonic. And yet, despite America's dominant position at a number of levels strategic, political-economic and ideational, there are plainly limits to US hegemony. These limits and the enduring strengths of American hegemony are revealed quite clearly in East Asia. This paper critically assesses a number of theories of hegemony, and argues that the concept continues to provide a useful way of conceptualising America's evolving relationship with East Asia. Theories of hegemony can, with appropriate caveats, also help us to understand the limits to Chinese and Japanese power in the region; two countries that are routinely cited as potential hegemonic rivals

Common E protein determinants for attenuation of glycosaminoglycan-binding variants of Japanese encephalitis and West Nile viruses

Natural isolates and laboratory strains of West Nile virus (WNV) and Japanese encephalitis virus (JEV) were attenuated for neuroinvasiveness in mouse models for flavivirus encephalitis by serial passage in human adenocarcinoma (SW13) cells. The passage variants displayed a small-plaque phenotype, augmented affinity for heparin-Sepharose, and a marked increase in specific infectivity for SW13 cells relative to the respective parental viruses, while the specific infectivity for Vero cells was not altered. Therefore, host cell adaptation of passage variants was most likely a consequence of altered receptor usage for virus attachment-entry with the involvement of cell surface glycosaminoglycans (GAG) in this process. In vivo blood clearance kinetics of the passage variants was markedly faster and viremia was reduced relative to the parental viruses, suggesting that affinity for GAG (ubiquitously present on cell surfaces and extracellular matrices) is a key determinant for the neuroinvasiveness of encephalitic flaviviruses. A difference in pathogenesis between WNV and JEV, which was reflected in more efficient growth in the spleen and liver of the WNV parent and passage variants, accounted for a less pronounced loss of neuroinvasiveness of GAG binding variants of WNV than JEV. Single gain-of-net-positive-charge amino acid changes at E protein residue 49, 138, 306, or 389/390, putatively positioned in two clusters on the virion surface, define molecular determinants for GAG binding and concomitant virulence attenuation that are shared by the JEV serotype flaviviruses.