血液单核细胞携带着具有多种表型的1型艾滋病毒毒株，包括巨噬细胞特异性CCR5病毒。

Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus.

作者信息

Xu Younong, Zhu Haiying, Wilcox Carrie K, van't Wout Angélique, Andrus Thomas, Llewellyn Nicholas, Stamatatos Leonidas, Mullins James I, Corey Lawrence, Zhu Tuofu

机构信息

Department of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington 98195-8070, USA.

出版信息

J Infect Dis. 2008 Jan 15;197(2):309-18. doi: 10.1086/524847.

DOI:10.1086/524847

PMID:18173363

Abstract

BACKGROUND

Recent studies have shown that blood monocytes harbor human immunodeficiency virus type 1 (HIV-1) variants that are genotypically distinguishable from those in CD4(+) T cells. However, the biological function of monocyte-derived HIV-1 remains unclear.

METHODS

Using pseudovirus assay, we analyzed the phenotype conferred by monocyte-derived HIV-1 envelopes from 8 patients.

RESULTS

All pseudoviruses carrying monocyte-derived HIV-1 envelopes used CCR5; however, their use of additional coreceptors delineated 4 phenotypes in which viruses used (1) CCR5 only, (2) CCR5 and CXCR4, (3) CCR3 and CCR5, or (4) multiple coreceptors, including CCR1, CCR3, GPR15, CCR5, and CXCR4. More importantly, we observed 2 distinct cell tropism phenotypes for pseudoviruses carrying monocyte-derived envelopes: (1) monocyte-derived, macrophage-specific R5 (MDMS-R5) virus that, using CCR5 only, could infect monocyte-derived macrophages (MDMs) but not CD4(+) T cells and (2) dual tropic virus that infected both MDMs and primary CD4(+) T cells. We found blood monocytes harboring viruses with multiple phenotypes as early as 25 days before seroconversion and as late as 9 years after seroconversion.

CONCLUSIONS

These data suggest that HIV-1 circulating in blood monocytes represents diverse HIV-1 with multiple phenotypes and that MDMS-R5 viruses may play an important role in infection with and persistence of HIV-1 within the monocyte/macrophage lineage.

摘要

背景

近期研究表明，血液单核细胞携带有1型人类免疫缺陷病毒（HIV-1）变体，其基因型与CD4(+) T细胞中的变体可区分。然而，单核细胞衍生的HIV-1的生物学功能仍不清楚。

方法

我们使用假病毒测定法分析了8例患者单核细胞衍生的HIV-1包膜赋予的表型。

结果

所有携带单核细胞衍生的HIV-1包膜的假病毒均使用CCR5；然而，它们对其他共受体的使用界定了4种表型，其中病毒使用（1）仅CCR5，（2）CCR5和CXCR4，（3）CCR3和CCR5，或（4）多种共受体，包括CCR1、CCR3、GPR15、CCR5和CXCR4。更重要的是，我们观察到携带单核细胞衍生包膜的假病毒有2种不同的细胞嗜性表型：（1）单核细胞衍生的巨噬细胞特异性R5（MDMS-R5）病毒，仅使用CCR5，可感染单核细胞衍生的巨噬细胞（MDM）但不能感染CD4(+) T细胞；（2）双嗜性病毒，可感染MDM和原代CD4(+) T细胞。我们发现，早在血清转化前25天以及血清转化后9年，血液单核细胞中就携带有多种表型的病毒。