Abstract
9:00 AM Friday, February 18, 2000
746 Emerging Viral Diseases Revisited
RE Shope. Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX.
The 1992 Institute of Medicine Report “Emerging infections: microbial threats to health in the United States” called attention to newly recognized infections and the conditions under which emerging infections occur. Many emerging viral infections masquerade as known flavivirus diseases. Three examples are Venezuelan hemorrhagic fever, originally and still frequently diagnosed clinically as dengue hemorrhagic fever; Nipah virus infection in Malaysia, originally diagnosed as Japanese encephalitis; and West Nile fever in New York City, diagnosed as St. Louis encephalitis. There are lessons to be learned from these case studies. The clinical diagnosis of viral infections is often incorrect. The laboratory is essential for correct diagnosis. The laboratory requires time for confirmation of presumptive diagnosis. The press is appropriately named – it will press for information to be made public prematurely. Public health decisions made on insufficient scientific information can be costly. Active surveillance is needed to detect new viral diseases. New viral diseases will continue to emerge because of urbanization, increased travel and transport, modification of wildlife ecology, and changing farm practices. It is not possible to predict what will be the next emerging virus, but it can be taken as an article of faith that emergence will continue.
747 Neutrophil Respiratory Burst Oxidase in Host Defenses
RA Clark, Department of Medicine, University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, TX.
The ability of neutrophils to kill invading microorganisms is largely dependent on a multi-component superoxide-generating NADPH oxidase that is activated during phagocytosis. In the genetic disorder chronic granulomatous disease (CGD), absent oxidase function results in recurrent and life-threatening infections. The components of this enzyme system include the gp91φox and p22φox subunits of cytochrome b559 in the plasma membrane and the soluble cytosolic proteins p47φox, p67φox, and Rac1/2. Interactions among these proteins occur through specific regions, including SH3 domains and proline-rich motifs. Stimulus-dependent activation requires translocation of cytosolic components to the membrane with assembly of a catalytic complex that shuttles electrons from cytosolic NADPH across the membrane to oxygen. The initial product, superoxide anion, and secondary products such as hydrogen peroxide, hydroxyl radical, and hypochlorous acid, accumulate within the phagocytic vacuole where they attack ingested microbes and are released from the cell where they may cause inflammatory tissue injury. Classical X-linked CGD results from mutations of the gp91φox gene, whereas the autosomal recessive form is caused by mutations of p47φox, or rarely p22φox or p67φox. Until very recently the phagocyte respiratory burst oxidase was the only mammalian member of the family of membrane-bound flavo-heme oxidoreductases. However, the detection of NADPH oxidase-like activities in certain non-myeloid cells and the recent discovery of a family of widely expressed human genes homologous to gp91φox raise the interesting possibility that systems analogous to the phagocyte oxidase carry out host defense and cell signaling functions in a broad range of tissues.