Study of HIV-1 transmission across cervical mucosa to tonsil tissue cells using an organ culture.

Study of HIV-1 transmission across cervical mucosa to tonsil tissue cells using an organ culture.
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DOI:
10.1111/aji.12018
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发表时间:
2013-01
期刊:
American journal of reproductive immunology (New York, N.Y. : 1989)
影响因子:
--
通讯作者:
Gupta P
Gupta P
中科院分区:
其他
文献类型:
--
作者:
Soto-Rivera J;Patterson BK;Chen Y;Shen C;Ratner D;Ding M;Tumne A;Gupta P

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SIV模型表明,当穿过宫颈阴道粘膜时,SIV/SIV感染的细胞迁移到局部淋巴结,在那里在全身病毒传播之前发生活跃的复制。本研究的目的是建立一个模型,研究HIV-1通过宫颈粘膜进入区域淋巴结后发生的早期传播事件。我们开发了一种器官培养模型,结合完整的宫颈组织外植体和扁桃体组织细胞作为替代引流淋巴组织。通过HIV-1 p24的产生、扁桃体细胞中病毒DNA和病毒RNA表达的定量来测量病毒复制。在该组合器官培养模型中,观察到无细胞和细胞相关的R5和X4嗜性HIV-1通过宫颈粘膜向扁桃体细胞的传播,如通过培养上清液中的HIV-1 p24所确定的,以及HIV-1前病毒DNA、HIV-1 p24 gag蛋白在CD 4+、CD 11 c+、CD 11 c+和CD 11 c+中的存在。CD 68+细胞和扁桃体细胞中表达HIV-1 mRNA的CD 45 RO + CD 4 T细胞的表达。此外,扁桃体细胞中HIV-1的共受体使用与HIV病毒的嗜性相关。我们的联合宫颈扁桃体器官培养可以作为一个实验模型,以研究HIV-1通过宫颈阴道粘膜传播到其近端淋巴结的最早阶段。
SIV model indicates that upon traversing the cervicovaginal mucosa, SIV/SIV-infected cells migrate to regional lymph nodes where active replication occurs prior to systemic virus dissemination. The purpose of the study is to develop a model to study early HIV-1 transmission events that occur after crossing the cervical mucosa into regional lymph nodes. We developed an organ culture model combining intact cervical tissue explants and tonsil tissue cells as the surrogate draining lymphoid tissue. Viral replication was measured by HIV-1 p24 production, quantification of viral DNA and viral RNA expression in tonsil cells. In this combined organ culture model transmission of cell-free and cell-associated R5- and X4-tropic HIV-1 through the cervical mucosa to tonsilar cells was observed as determined by HIV-1 p24 in culture supernatant, and the presence of HIV-1 proviral DNA, HIV-1 p24 gag protein in CD4+, CD11c+, CD68+ cells and expression of HIV-1 mRNA expressing CD45RO+ CD4 T cells in tonsil cells. Furthermore, co-receptor usage of HIV-1 in tonsil cells correlated with inoculating virus tropism. Our combined cervix-tonsil organ culture could serve as an experimental model to study the earliest stages of HIV-1 transmission through cervicovaginal mucosa to its proximal lymph nodes.
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