Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.
Early Colorectal Responses to HIV-1 and Modulation by Antiretroviral Drugs.
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DOI：
10.3390/vaccines9030231
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发表时间：
2021-03-08
期刊：
影响因子：
7.8
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Herrera C;McRaven MD;Laing KG;Dennis J;Hope TJ;Shattock RJ
急性HIV感染期间的先天反应与疾病进展和发病机制相关。然而，关于在粘膜传播部位感染的最初几个小时内发生的事件的信息有限。与离体HIV-1挑战模型的人结直肠组织，我们评估了粘膜反应诱导的R5和X4嗜性HIV-1分离株在第一个24小时的曝光。显微镜研究表明，在接种后6小时内，病毒穿透至固有层达39 μm。在暴露于R5或X4嗜性分离株后，观察到激发后6 h炎性细胞因子、趋化因子、干扰素- γ（IFN-γ）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的分泌水平快速增加。该特征在24 h的较晚时间点持续存在。然而，与R5嗜性分离株相比，暴露于X4嗜性分离株在蛋白质组和转录组水平上诱导了更大的变化。与R5-HIV-1相比，X4-分离株诱导了更高水平的CCR 5配体（RANTES、MIP-1α和MIP-1β）分泌。结直肠杀微生物剂的潜在候选药物，包括进入，融合或逆转录酶抑制剂表现出不同的能力来调节这些反应。我们的研究结果表明，在结直肠组织中，炎症反应和Th 1细胞因子在病毒暴露后的第一个24小时内诱导。
Innate responses during acute HIV infection correlate with disease progression and pathogenesis. However, limited information is available about the events occurring during the first hours of infection in the mucosal sites of transmission. With an ex vivo HIV-1 challenge model of human colorectal tissue we assessed the mucosal responses induced by R5- and X4-tropic HIV-1 isolates in the first 24 h of exposure. Microscopy studies demonstrated virus penetration of up to 39 μm into the lamina propia within 6 h of inoculation. A rapid, 6 h post-challenge, increase in the level of secretion of inflammatory cytokines, chemokines, interferon- γ (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed following exposure to R5- or X4-tropic isolates. This profile persisted at the later time point measured of 24 h. However, exposure to the X4-tropic isolate tested induced greater changes at the proteomic and transcriptomic levels than the R5-tropic. The X4-isolate induced greater levels of CCR5 ligands (RANTES, MIP-1α and MIP-1β) secretion than R5-HIV-1. Potential drugs candidates for colorectal microbicides, including entry, fusion or reverse transcriptase inhibitors demonstrated differential capacity to modulate these responses. Our findings indicate that in colorectal tissue, inflammatory responses and a Th1 cytokine profile are induced in the first 24 h following viral exposure.
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影响因子：
4.9
作者：
Biswas, Nabanita;Rodriguez-Garcia, Marta;Wira, Charles R.
通讯作者：
Wira, Charles R.
影响因子：
3.7
作者：
Francis SC;Hou Y;Baisley K;van de Wijgert J;Watson-Jones D;Ao TT;Herrera C;Maganja K;Andreasen A;Kapiga S;Coulton GR;Hayes RJ;Shattock RJ
通讯作者：
Shattock RJ
影响因子：
7.4
作者：
Grivel JC;Shattock RJ;Margolis LB
通讯作者：
Margolis LB
影响因子：
5.4
作者：
Gordon, CJ;Muesing, MA;Trkola, A
通讯作者：
Trkola, A
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.