共 53 条
Identification of sequential viral escape mutants associated with altered T-cell responses in a human immunodeficiency virus type 1-infected individual
被引:58
作者:

Geels, MJ
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Cornelissen, M
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Schuitemaker, H
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Anderson, K
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Kwa, D
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Maas, J
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Dekker, JT
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Baan, E
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Zorgdrager, F
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

van den Burg, R
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

van Beelen, M
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Lukashov, VV
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Fu, TM
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Paxton, WA
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

van der Hoek, L
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Dubey, SA
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Shiver, JW
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands

Goudsmit, J
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机构: Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands
机构:
[1] Univ Amsterdam, Dept Human Retrovirol, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands
[2] Univ Amsterdam, Sanquin Res CLB, NL-1012 WX Amsterdam, Netherlands
[3] Univ Amsterdam, Landsteiner Lab, NL-1012 WX Amsterdam, Netherlands
[4] Ctr Poverty Related Communicable Dis, Amsterdam, Netherlands
[5] Merck Res Labs, Dept Virus & Cell Biol, West Point, PA USA
关键词:
D O I:
10.1128/JVI.77.23.12430-12440.2003
中图分类号:
Q93 [微生物学];
学科分类号:
071005 ;
100705 ;
摘要:
Control of viremia in natural human immunodeficiency virus type 1 (HIV-1) infection in humans is associated with a virus-specific T-cell response. However, still much is unknown with regard to the extent of CD8(+) cytotoxic T-lymphocyte (CTL) responses required to successfully control HIV-1 infection and to what extent CTL epitope escape can account for rises in viral load and ultimate progression to disease. In this study, we chose to monitor through full-length genome sequence of replication-competent biological clones the modifications that occurred within predicted CTL epitopes and to identify whether the alterations resulted in epitope escape from CTL recognition. From an extensive analysis of 59 biological HIV-1 clones generated over a period of 4 years from a single individual in whom the viral load was observed to rise, we identified the locations in the genome of five CD8(+) CTL epitopes. Fixed mutations were identified within the p17, gp120, gp41, Nef, and reverse transcriptase genes. Using a gamma interferon ELIspot assay, we identified for four of the five epitopes with fixed mutations a complete loss of T-cell reactivity against the wild-type epitope and a partial loss of reactivity against the mutant epitope. These results demonstrate the sequential accumulation of CTL escape in a patient during disease progression, indicating that multiple combinations of T-cell epitopes are required to control viremia.
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页码:12430 / 12440
页数:11
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