A mutation in human immunodeficiency virus reverse transcriptase and decline in CD4 lymphocyte numbers in long-term zidovudine recipients.

A mutation in human immunodeficiency virus reverse transcriptase and decline in CD4 lymphocyte numbers in long-term zidovudine recipients.
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长期齐多夫定接受者的人类免疫缺陷病毒逆转录酶突变和 CD4 淋巴细胞数量下降。

DOI:
10.1093/infdis/167.3.526
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发表时间:
1993
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Merigan,TC
Merigan,TC
中科院分区:
--
文献类型:
--
作者:
Kozal,MJ;Shafer,RW;Winters,MA;Katzenstein,DA;Merigan,TC

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使用嵌套聚合酶链反应测定来定义来自外周血单个核细胞(PBMC)的DNA中的人类免疫缺陷病毒(HIV)多基因的特定密码子,氨基酸215的序列和来自38名接受齐多夫定治疗的患者的血清中的病毒RNA的序列。平均治疗34个月后,密码子215突变序列的17例患者CD4细胞平均减少50%,而密码子215野生型序列的21例患者CD4细胞平均增加11% (P< 0.0001)。突变为215的患者在PBMC中有9倍高的原病毒负担。检测血浆病毒RNA中密码子215突变先于检测PBMC DNA突变和CD4细胞下降。在接受齐多夫定治疗的患者中,HIV逆转录酶基因密码子215突变的出现可能是即将到来的免疫衰退的标志。
A nested polymerase chain reaction assay was used to define the sequence of a specific codon, amino acid 215, of the human immunodeficiency virus (HIV)polgene in DNA from peripheral blood mononuclear cells (PBMC) and viral RNA from serum from 38 patients treated with zidovudine for ⩾2 years. After treatment for a mean of 34 months, 17 patients with sequences with a codon 215 mutation had a mean 50% decrease in CD4 cells, compared with 21 patients with sequences wild-type at codon 215, who had a mean 11% increase in CD4 cells (P< .0001). Patients with a mutation at 215 had a ninefold higher provirus burden in PBMC. Detection of the codon 215 mutation in plasma viral RNA preceded detection of the mutation in DNA from PBMC and decline in CD4 cells. The appearance of a mutation at codon 215 in the HIV reverse transcriptase gene in patients receiving zidovudine may be a marker for impending immunologic decline.
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