1988 Fiscal Year Final Research Report Summary
Pathology of cells induced by paramyxovirus infection
| Project/Area Number |
60440036
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | Institute for Molecular and Cellular Biology, Osaka University (1985-1986, 1988)
Tokyo Institute of Technology (1987) |
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Principal Investigator |
OKADA Y. Professor Institute for Molecular and Cellular Biology, Osaka Univ., 細胞工学センター, 教授 (30029756)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMA Yasufumi Research Assistant Department of Fermentation techmnology, Facuty of Engineering, 工学部, 助手 (50187423)
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| Project Period (FY) |
1985 – 1988
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| Keywords | cDNA of F and HANA / fusion / naked lipid bilayer / cDNA / 限定分解 / 毒性 |
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| Research Abstract |
1. Mechanism of cell fusion by HVJ: On the basis of our experimental data, a hypothesis of the mechanism has been presented. After adsorption of HVJ onto cells, Fl N-terminal fusogenic domain inserted into cell membranes udergo conforma-tional change at 37゜C. This results in the folding in cholesterol molecule and the perturbation of the lipid bilayer, followed by marked damage of the cell mem-brane. This damage in turn induces disarragement of the cytoskeletal system, caused by the sudden introduction of Ca ions into the cytoplasm, and allows the membrane proteins to become freely mobile. The naked lipid bilayers formed by the clustering of IMP(Intramembrane particle) can then come into direct contact without interference from IMPs. In thee areas of attachment the cell membranes promptly fuse. Thus, the fundamental mechanism of cell fusion by HVJ seems to be similar to the fusion mechanism by PEG, electroporation and microsurgery of cell membranes.
2. This presentation is supported by
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the finding as follows: It has been demon-strated that aged HVJ virions easily fuse together by collision, but young ones immediately after the budding from infected cells show resistancy to this kind of fusion. It has been know that IMP are aggregated together in the envelope of aged virions, because of the disruption of the connection with M protein.
3. Simple liposomes can fuse with cells fusing together: It has been reported that liposomes containing diphtheria toxin fragment A show the activity of selective killing of HIV infected cells fusing with B-lymphocytes. It is possible to condiser that naked lipid bilayers are exposed on these cell surfaces and the liposomes become able to fuse with the areas.
4. cDNA of F and HANA glycoproteins have been isolated from HVJ or NDV infected cells. These cDNA plasmids containing SV40 ori showed high expressions when intro-duced in COS cells. Now expression of plasmids containing these cDNA and actin promoter are being observed in LLCMK2, CV1 and L cells. This project has not yet completed. Less
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