2003 Fiscal Year Final Research Report Summary
Cytotoxic T lymphocytes and viral mutations in HTLV-I-associated myelopathy
| Project/Area Number |
14570610
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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 |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
KUBOTA Ryuji Kagoshima University, Faculty of Medicine, Associate professor, 医学部, 助教授 (70336337)
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| Co-Investigator(Kenkyū-buntansha) |
OSAME Mitsuhiro Kagoshima University, Graduate School of Medical and Dental Sciences, 大学院・医歯学総合研究科, 教授 (10041435)
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| Project Period (FY) |
2002 – 2003
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| Keywords | HTLV-I / HTLV-I-associated myelopathy / cytotoxic T lymphocyte / mutant virus / viral evolution / 非同義置換 |
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| Research Abstract |
Patients with HTLV-I-associated myelopathy(HAM)have high proviral load despite vigorous cytotoxic T lymphocytes(CTL)responses to the virus.To elucidate whether HTLV-I-speciflc CTL eliminate HTLV-I in vivo in patients with HAM and whether a mutant virus emerges and predominates during the time course in the patients, we performed a longitudinal analysis of HTLV-I proviral load, frequency and degeneracy of HTLV-I Tax specific CTL, viral sequence, and frequency of mutant virus-specific CTL in three patients with HAM.Frequency and degeneracy of CTL paralleled with the proviral load in the patients.Positive pressures were detected in 3 out of 6 sequences associated with the known CTL epitopes by analyzing synonymous and non-synonymous substitutions of viral sequences.The rate of naturally occurring mutant virus ranged from 0 to 20% in each patient, however, no mutant virus accumulated during the time course even if the virus was not recognized by the CTL. These data suggest that CTL in fact eliminate HTLV-J in vivo and that no escape variant of HTLV-I predominates during the time course.This implies that these CTL epitopes can be targets for vaccine development.
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