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来自围产期传播配对的HIV-1变体在扁桃体组织和外周血单核细胞中表现出相似的遗传和复制特性。

HIV-1 variants from a perinatal transmission pair demonstrate similar genetic and replicative properties in tonsillar tissues and peripheral blood mononuclear cells.

作者信息

Gray Laurie, Fiscus Susan, Shugars Diane

机构信息

Dental Research Center, University of North Carolina School of Dentistry, Chapel Hill, North Carolina 27599, USA.

出版信息

AIDS Res Hum Retroviruses. 2007 Sep;23(9):1095-104. doi: 10.1089/aid.2006.0247.

Abstract

Human immunodeficiency virus type 1 (HIV-1) can be acquired through oropharyngeal tissues in breastfeeding infants. Efforts to better understand the determinants of breast milk transmission are hampered by the lack of a relevant oral human mucosa model and well-defined breast milk-derived viruses. This study used human ex vivo palatine tonsil tissues and peripheral blood mononuclear cells (PBMCs) to characterize the genetic, biological, and replicative properties of HIV-1 variants obtained from a perinatal transmission pair. Unique viral populations from maternal breast milk and infant blood were identified by gp120 V1-V2- and V3-specific heteroduplex tracking assays (HTAs). Full-length infectious recombinant viruses, containing a common HIV-1 NL4-3 genetic background, were generated with V1-V3 gp120 fragments from maternal and infant isolates representing the major viral populations identified in the HTAs. The resulting recombinant viruses used the CCR5 coreceptor, were nonsyncytium forming, and demonstrated replication properties similar to those of parental and control viruses in PBMCs and tonsillar explants. These findings indicate that viruses from breast milk cells and infant blood can infect PBMCs and tonsil tissues. The maternal and infant HIV-1 viruses detailed here will provide useful tools for defining the viral and host factors that contribute to HIV breastfeeding transmission.

摘要

1型人类免疫缺陷病毒(HIV-1)可通过母乳喂养婴儿的口咽组织传播。由于缺乏相关的口腔人类黏膜模型以及定义明确的母乳衍生病毒,更好地了解母乳传播决定因素的努力受到了阻碍。本研究使用人类离体腭扁桃体组织和外周血单核细胞(PBMC)来表征从一对围产期传播病例中获得的HIV-1变体的遗传、生物学和复制特性。通过gp120 V1-V2和V3特异性异源双链追踪分析(HTA)鉴定了来自母乳和婴儿血液的独特病毒群体。利用来自母婴分离株的V1-V3 gp120片段,构建了具有常见HIV-1 NL4-3遗传背景的全长感染性重组病毒,这些片段代表了HTA中鉴定出的主要病毒群体。产生的重组病毒利用CCR5共受体,不形成合胞体,并且在PBMC和扁桃体外植体中表现出与亲本病毒和对照病毒相似的复制特性。这些发现表明,来自母乳细胞和婴儿血液的病毒可以感染PBMC和扁桃体组织。本文详细描述的母婴HIV-1病毒将为确定导致HIV母乳喂养传播的病毒和宿主因素提供有用的工具。

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