1987 Fiscal Year Final Research Report Summary
Shutoff of host protein synthesis during infection by influenza A virus
| Project/Area Number |
61480152
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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 | Nihon University School of Medicine |
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Principal Investigator |
SHIMIZU Kazufumi Nihon University School of Medicine, 医学部, 助教授 (50004677)
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| Co-Investigator(Kenkyū-buntansha) |
MIZUMOTO Kiyohisa Institute of Medical Science, University of Tokyo, 医学科研究所, 助教授 (80092344)
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| Project Period (FY) |
1986 – 1987
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| Keywords | InfluenzaA virus / Temperature-sensitive (ts) mutant / Shutoff / Heat shock / Sodium arsenite / Cadmium chloride |
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| Research Abstract |
1. Influenza A virus genes which are responsible for the shutoff of the host protein synthesis. (1) The protein synthesis of MDCK cells infected with temperature-sensitive (ts) mutants of influenza A virus was analyzed to identify the virus genes involved in the shutoff. Several mutants having ts mutation on the PB1, PB2, PA, or NS1 gene, respectively, failed to shutoff the host protein synthesis at the restrictive temperature of 40゜C. This indicated that these genes are involved in the shutoff mechanism. (2) The majority of the above ts mutants also failed to fully induce the synthesis of the late viral proteins (HA and M), suggesting that PB1, PB2, PA, and NS1 genes play a role on stimulating the synthesis of the late proteins. (3) Analysis of the PB2-ts mutants revealed that the PB2 protein participates not only in the synthesis of viral RNAs but also in the regulatory mechanisms operating on the synthesis of mRNAs and cRNAs of the three polymerase genes (PB1, PB2, and PA). (4) Anal
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ysis of the NS1 ts mutants demonstrated that the NS1 protein does not affect virion RNA transcriptase activity but does the synthesis of cRNAs, vRNAs, and secondary mRNAs in the infected cells. It was also shown that the NS1 protein is involved in increasing the efficiency of translaton of mRNAs for the HA and M proteins during late phase of infection. 2. Mechanisms of the shutoff of host protein synthesis. (1) Analysis of the-functional mRNAs in the cytoplasm of virus-infected cells revealed that the lebels of mRNAs for host proteins are not significantly changed during infection even after the shutoff of host protein synthesis. This means that the shutoff occurs at the translational stages. (2) As the opposite effect, the synthesis of the viral proteins was found to be suppressed at the translational stages in association with the induction of host stress proteins (hsp) by heat shock, sodium arsenite, or cadmium chloride. Influenza A virus-infection seems to cause a modification of translational machinary, for which it competes with hsp inducers, and , thereby, to lead preferential translation of the viral mRNAs. Less
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