1992 Fiscal Year Final Research Report Summary
Hypothesis: Both appearance and disappearance of viruses are controlled by the accumulation of amino acid substitution in receptor binding domain
| Project/Area Number |
02454184
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | National Institute of Health |
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Principal Investigator |
TAKEDA Naokazu National Institute of Health, Department of Epidemiology, Chief, 感染症疫学部, 室長 (90132894)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Shudo National Institute of Health, Deputy Director General, 副所長 (20072902)
MIYAMURA Kikuko National Institute of Health, Department of Epidemiology, Chief, 感染症疫学部, 室長 (40072897)
TANIMURA Masako National Children's Medical Research Center, 小児生態部, 研究員 (90014191)
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| Project Period (FY) |
1990 – 1992
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| Keywords | Picornaviruses / Enterovirus 70 / Molecular evolution / Phylogenetic tree / Nucleotide substitution / Receptor |
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| Research Abstract |
The genome of the RNA viruses is known to evolve 10^6 times faster than ordinary DNA genome. This higher evolutionary rate is thought to be linked with both appearance and disappearance of the viruses in human world. To understand the interaction between cellular receptor molecule and receptor binding domain of the virion the nucleotide and amino acid substitutions in virus encoded proteins were analyzed. According to the nucleotide sequences of EV70 capsid protein VP1 we have constructed a fine phylogenetic tree. By analyzing the phylogenetic relationship and the substitution pattern among the isolates we deduced the original nucleotide sequence. The evolutionary rate was estimated to be 5x10^<-3>/site/year, whereas the rate of the 3C protease region of coxsackievirus A24 variant, an another agent that cause acute hemorrhagic conjunctivitis, was calculated to be 4.9x10^<-3>/site/year. Using a monoclonalantibody that is capable of blocking EV70 infection screening of the COS cells transfected with cDNA library derived from Hela cell mRNA was carried out by socalled "panning" method. The receptor molecules are found to be located on the surface of the susceptive cells and has the nucleotide sequence identical to that of the molecule which regulates a function of an immunologically important molecule.
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