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埃塞俄比亚艾滋病患者中HIV-1 C亚型的合胞体诱导型和非合胞体诱导型表型及共受体使用情况

HIV-1 subtype C syncytium- and non-syncytium-inducing phenotypes and coreceptor usage among Ethiopian patients with AIDS.

作者信息

Abebe A, Demissie D, Goudsmit J, Brouwer M, Kuiken C L, Pollakis G, Schuitemaker H, Fontanet A L, Rinke de Wit T F

机构信息

Ethiopian-Netherlands AIDS Research Project, Ethiopian Health and Nutrition Research Institute, Addis Ababa.

出版信息

AIDS. 1999 Jul 30;13(11):1305-11. doi: 10.1097/00002030-199907300-00006.

DOI:10.1097/00002030-199907300-00006
PMID:10449282
Abstract

OBJECTIVE

To assess syncytium-inducing (SI) and non-syncytium-inducing (NSI) frequencies, coreceptor usage and gp120 V3 sequences of HIV-1 isolates from Ethiopian AIDS patients.

PATIENTS

Cross-sectional study on 48 hospitalized AIDS patients (CD4 T cells < 200 x 10(6) cell/l) with stage III or IV of the WHO staging system for HIV-1 infection and disease.

METHODS

Peripheral blood mononuclear cells (PBMC) from all 48 patients were tested by MT-2 assay to determine SI/NSI phenotypes. Lymphocyte subsets were enumerated using Coulter counting and FACScan analysis. Viral load determination used a nucleic acid sequence-based amplification assay (NASBA). Coreceptor usage of HIV-1 biological clones was measured using U87 CD4/chemokine receptor transfectants and phytohemagglutinin-stimulated PBMC of healthy donors with wild-type CCR5 and homozygous mutation CCR5delta32 (a 32 base-pair deletion in CCR5). Reverse transcriptase polymerase chain reaction sequencing was performed on the third variable region (V3) of the HIV-1 gene gp120. Sequence alignments were done manually; phylogenetic analyses used PHYLIP software packages.

RESULTS

SI viruses were detected for 3/48 (6%) AIDS patients only. Lower mean absolute CD4 counts were determined in patients with SI virus compared with NSI (P = 0.04), but no differences in viral load were observed. All patients were found to be infected with HIV-1 subtype C, based on V3 sequencing. NSI biological clones used CCR5 as coreceptor; SI biological clones used CXCR4 and/or CCR5 and/or CCR3.

CONCLUSIONS

Ethiopian patients with HIV-1 C-subtype AIDS harbour a remarkably low frequency of SI phenotype viruses. Coreceptor usage of these viruses correlates with their biological phenotypes.

摘要

目的

评估来自埃塞俄比亚艾滋病患者的HIV-1分离株的合胞体诱导(SI)和非合胞体诱导(NSI)频率、共受体使用情况及gp120 V3序列。

患者

对48例住院艾滋病患者(CD4 T细胞<200×10⁶细胞/升)进行横断面研究,这些患者处于世界卫生组织HIV-1感染和疾病分期系统的III期或IV期。

方法

采用MT-2试验检测所有48例患者的外周血单个核细胞(PBMC),以确定SI/NSI表型。使用库尔特计数法和FACScan分析法对淋巴细胞亚群进行计数。病毒载量测定采用基于核酸序列扩增的检测方法(NASBA)。使用U87 CD4/趋化因子受体转染细胞以及来自具有野生型CCR5和纯合突变CCR5delta32(CCR5基因中32个碱基对缺失)的健康供体的植物血凝素刺激的PBMC,来测定HIV-1生物学克隆的共受体使用情况。对HIV-1基因gp120的第三个可变区(V3)进行逆转录酶聚合酶链反应测序。序列比对通过手工完成;系统发育分析使用PHYLIP软件包。

结果

仅在3/48(6%)的艾滋病患者中检测到SI病毒。与NSI患者相比,SI病毒患者的平均绝对CD4计数更低(P = 0.04),但病毒载量未观察到差异。基于V3测序,所有患者均被发现感染HIV-1 C亚型。NSI生物学克隆使用CCR5作为共受体;SI生物学克隆使用CXCR4和/或CCR5和/或CCR3。

结论

埃塞俄比亚HIV-1 C亚型艾滋病患者中SI表型病毒的频率极低。这些病毒的共受体使用情况与其生物学表型相关。

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