|Budget Amount *help
¥3,300,000 (Direct Cost : ¥3,300,000)
Fiscal Year 2003 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 2002 : ¥2,500,000 (Direct Cost : ¥2,500,000)
Possible involvement of cytoskeletal components in the rabies virus replication process was investigated from various view points. Experimental results obtained so far strongly suggested that moesin, one of the ERM family proteins which work as the molecular linker between the actin filament and membrane anchor protein, interacts with the viral glycoprotein (G) directly. In the amino acid sequence of the cytoplasmic domain of the viral G protein as well as CD44, CD43 and ICAM I, we found a small homologous basic region, locating beneath the cell membrane, which seemed to be involved in their direct binding to moesin. This interaction was also suggested to be involved in gradual dissociation of cellular microvilli in progression of rabies virus replication process. Immunoelectron microscopic studies revealed that cytoskeletal components were detected in limited sites in or on the virion, that is, they were detected mostly at the hem of the bullet-shaped virion, and the minor were near the head of the virion. Based on these observations, we speculate that the actin-based cytoskeleton system is involved in the virion formation by budding process as following: formation of a small initial dome ("a bud" of the virion) composed of envelope proteins on the cell surface is dependent on the vertical force generated by the membrane-cytoskeleton system (actin-CD44 system), which might work against the horizontal force of surface tension of cell membrane. After elongation of the virion, it should be pinched off from the membrane, for which the energy-supplying membrane cytoskeleton,system might also be involved.