| Project/Area Number |
61480151
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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 | Tokyo Metropolitan Institute of Medical Science (1987)
The University of Tokyo (1986) |
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Principal Investigator |
NOMOT Akio Tokyo Metropolitan Institute of Medical Science, 微生物研究部門, 部長 (70112670)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | Type 1 poliovirus / Gene expression / Neurovirulence / Infectious cDNA clone / 5' noncoding region / Functional structure of RNA / 人工変異株ウィルス / 1型ポリオウイルス / 感染性cDNAクローン / 5′noncoding領域 / 人工変異株ウイルス / 5'noncoding領域 |
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| Research Abstract |
The attenuated Sabin 1 strain was derived from the virulent Mahoney strain of type 1 polioveirus by multiple passages through host cells of nonhuman origin. Elucidation of total nucleotide sequence of the genomes of both the strain revealed 55 nucleotide substitutions within 7441 total nucleotides of the genome without poly(A) at the 3' terminus. These nucleotide changes were found to be scattered over the entire length of the genome and resulted in 21 amino-acid replacements within the viral polyprotein. To identify the mutation(s) influencing neurovirulence of type 1 poliovirus, we constructed a number of recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains by using infectious cDNA clones of both the strain genomes. These recombinant viruses were tested for their monkey neurovirulence. As a result, the genome region strongly influencing neuroviruluence of type 1 poliovirus was identified to be the 5' noncoding sequence. Of the mutations the 5' noncoding sequence, adenine residue at nucleotide position 480 appeared to importantly influence neurovirulent phenotype. Therefore, it is possible that only one nucleotide change (A - G) at nucleotide position 480 functions like a switch determining which of these two phenotype, neurovirulent or attenuated phenotype in regard with gene function of the 5' noncoding sequence. However, introduction of guanine residue at the position in the Mahoney sequence was not sufficient for the virus to show the attenuation phenotype expected. These results suggested that functional structure formed in the 5' noncoding region referring to the experssion of attenuation phenotype is not attributed to the primary structure in the vicinity of position 480 but to the highly- ordered structure influenced by the nucleotide at position 480.
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