Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue.
Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue.
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DOI：
10.1084/jem.20022212
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发表时间：
2004-04-19
影响因子：
15.3
通讯作者：
Shattock, RJ
中科院分区：
文献类型：
--
作者：
Hu, QX;Frank, I;Williams, V;Santos, JJ;Watts, P;Griffin, GE;Moore, JR;Pope, M;Shattock, RJ
识别参与HIV-1在粘膜表面进入和传播的细胞因子对于理解病毒发病机制和制定有效的预防策略至关重要。在这里，我们描述了对HIV-1进入抑制剂预防离体人类宫颈组织感染和传播的能力的评估。单独阻断CD 4或CCR 5和CXCR 4共同阻断可抑制局部粘膜感染。然而，需要同时阻断CD 4和甘露糖结合C型凝集素受体，包括树突状细胞特异性细胞间粘附分子抓取整合素，以抑制迁移细胞对HIV-1的摄取和传播。相反，通过中和mAb b12和CD 4-IgG 2（PRO-542）直接靶向HIV-1阻断了局部感染和病毒传播途径。迁移细胞的流式细胞术分析和免疫染色显示了两个主要群体，CD 3 +HLA-DR−和CD 3 −HLA-DR+细胞，后者中有很大比例也表达树突状细胞特异性细胞间粘附分子抓取整合素。珠耗尽研究表明，这样的HLA-DR+细胞占高达90%的HIV-1传播。使用未成熟单核细胞衍生的树突状细胞的其他研究表明，虽然甘露糖结合C型凝集素受体和CD 4是gp 120的主要受体，但其他机制可能是病毒捕获的原因。我们鉴定的主要受体参与HIV-1感染和人类宫颈组织内的传播突出了杀微生物剂开发的重要目标。
Identification of cellular factors involved in HIV-1 entry and transmission at mucosal surfaces is critical for understanding viral pathogenesis and development of effective prevention strategies. Here we describe the evaluation of HIV-1 entry inhibitors for their ability to prevent infection of, and dissemination from, human cervical tissue ex vivo. Blockade of CD4 alone or CCR5 and CXCR4 together inhibited localized mucosal infection. However, simultaneous blockade of CD4 and mannose-binding C-type lectin receptors including dendritic cell–specific intercellular adhesion molecule–grabbing integrin was required to inhibit HIV-1 uptake and dissemination by migratory cells. In contrast, direct targeting of HIV-1 by neutralizing mAb b12 and CD4-IgG2 (PRO-542) blocked both localized infection and viral dissemination pathways. Flow cytometric analysis and immunostaining of migratory cells revealed two major populations, CD3+HLA-DR− and CD3−HLA-DR+ cells, with a significant proportion of the latter also expressing dendritic cell–specific intercellular adhesion molecule–grabbing integrin. Bead depletion studies demonstrated that such HLA-DR+ cells accounted for as much as 90% of HIV-1 dissemination. Additional studies using immature monocyte-derived dendritic cells demonstrated that although mannose-binding C-type lectin receptors and CD4 are the principal receptors for gp120, other mechanisms may account for virus capture. Our identification of the predominant receptors involved in HIV-1 infection and dissemination within human cervical tissue highlight important targets for microbicide development.
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影响因子：
5.4
作者：
Frank, I;Piatak, M;Pope, M
通讯作者：
Pope, M
影响因子：
1.5
作者：
ALLAWAY, GP;DAVISBRUNO, KL;MADDON, PJ
通讯作者：
MADDON, PJ
影响因子：
56.9
作者：
BURTON, DR;PYATI, J;BARBAS, CF
通讯作者：
BARBAS, CF
DOI：
10.1073/pnas.96.10.5698
发表时间：
1999-05-11
影响因子：
11.1
作者：
Baba, M;Nishimura, O;Fujino, M
通讯作者：
Fujino, M
影响因子：
5.5
作者：
Chehimi, J;Luo, Q;Montaner, LJ
通讯作者：
Montaner, LJ