Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus.
Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus.
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DOI：
10.1086/524847
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发表时间：
2008-01
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影响因子：
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通讯作者：
Younong Xu;Haiying Zhu;Carrie K. Wilcox;A. V. van’t Wout;Thomas Andrus;N. Llewellyn;L. Stamatatos;J. Mullins;L. Corey;Tuofu Zhu
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作者：
Younong Xu;Haiying Zhu;Carrie K. Wilcox;A. V. van’t Wout;Thomas Andrus;N. Llewellyn;L. Stamatatos;J. Mullins;L. Corey;Tuofu Zhu
背景最近的研究表明，血液单核细胞含有人类免疫缺陷病毒1型（HIV-1）变异体，其基因型与CD4（+）T细胞中的变异体不同。然而，单核细胞来源的HIV-1的生物学功能仍不清楚。方法 使用假病毒检测，我们分析了 8 名患者的单核细胞来源的 HIV-1 包膜所赋予的表型。结果 所有携带单核细胞来源的 HIV-1 包膜的假病毒均使用 CCR5；然而，他们使用额外的辅助受体描绘了 4 种表型，其中病毒使用 (1) 仅 CCR5，(2) CCR5 和 CXCR4，(3) CCR3 和 CCR5，或 (4) 多个辅助受体，包括 CCR1、CCR3、GPR15、CCR5 和 CXCR4。更重要的是，我们观察到携带单核细胞来源的包膜的假病毒有两种不同的细胞向性表型：（1）单核细胞来源的巨噬细胞特异性R5（MDMS-R5）病毒，仅使用CCR5，可以感染单核细胞来源的巨噬细胞（MDM），但不能感染CD4（+）T细胞；（2）双嗜性病毒，既感染MDM又感染原代CD4（+）T细胞。我们早在血清转化前 25 天、晚至血清转化后 9 年就发现血液单核细胞含有多种表型的病毒。结论 这些数据表明，血液单核细胞中循环的 HIV-1 代表具有多种表型的多种 HIV-1，MDMS-R5 病毒可能在单核细胞/巨噬细胞谱系中 HIV-1 的感染和持续存在中发挥重要作用。
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.