1998 Fiscal Year Final Research Report Summary
Analysis of hepatitis C virus genome variability and its relation to host immune system recognition
| Project/Area Number |
09670479
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
KASHIWAGI Seizaburo Kyushu University Department Professor, 医学部, 教授 (70038826)
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| Co-Investigator(Kenkyū-buntansha) |
NABESHIMA Shigeki Kyushu University Department assistant, 医学部, 助手 (50304796)
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| Project Period (FY) |
1997 – 1998
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| Keywords | hepatitis C virus / chronic infection / gene / hypervariable region / immune complex / Immune Complex |
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| Research Abstract |
The mechanism by which the hepatitis C virus (HCV) evade the host immune system and establishes chronic infection is of major interest in medicine. A region of the HCV genome in which the nucleotide sequence is highly divergent among isolates is termed the hypervariable region (HVR). It is postulated that the diversity and variability of HVR allows HCV to evade the host immune system.
To investigate this hypothesis, we determined the HCV nucleotide and amino acid sequences through RT-PCR and cloning. The replacement to silent mutation ratio (R/S) was very low in the core and NS5A regions, suggesting selective pressure for preserved sequences. In contrast, R/S in HVR was equivalent to that occurs randomly. These results did not support the hypothesis.
The HVR nucleotide sequences were determined in free and immunecomplex formed HCV.Although HVR sequences were segregated in some patients, identical sequences were found in both free and IC formed HCV.The HVR sequences found in the IC formed HCV were also found in free and/or IC formed HCV one year later in many patients. These results suggested that changes in the HVR sequence are not necessary for the establishment of chronic HCV infection.
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