Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors.
Efficient interaction of HIV-1 with purified dendritic cells via multiple chemokine coreceptors.
复制标题
DOI：
10.1084/jem.184.6.2433
复制
发表时间：
1996-12-01
期刊：
影响因子：
--
通讯作者：
Steinman RM
中科院分区：
文献类型：
--
作者：
Granelli-Piperno A;Moser B;Pope M;Chen D;Wei Y;Isdell F;O'Doherty U;Paxton W;Koup R;Mojsov S;Bhardwaj N;Clark-Lewis I;Baggiolini M;Steinman RM
HIV-1 在树突状细胞 (DC)-T 细胞共培养物中活跃复制，但很难证明纯化的成熟 DC 的实质性感染。我们现在发现，尽管 T 细胞具有更高水平的 CD4 和 gp120 结合，但 HIV-1 在 DC 中比 T 细胞更有效地开始逆转录。从皮肤或血液前体中分离的 DC 具有类似的行为。通过 37°C 90 分钟病毒脉冲后逆转录早期产物的逐渐形成来评估，几种 M 向性菌株和 T 向性菌株 IIIB 有效进入 DC。然而，很少检测到含有晚期gag的序列，因此不会发生活跃的病毒复制。这些早期转录本的形成似乎是在 HIV-1 进入之后形成的，而不是在包含病毒 DNA 的病毒粒子结合之后形成的。如果 DC 在冰上暴露于病毒 4 小时，或在 37°C 下暴露于病毒 90 分钟（允许病毒结合的条件），则早期转录物很少。此外，早期转录本一旦形成，对胰蛋白酶不敏感。 M-tropic 分离株的进入被趋化因子 RANTES 阻断，IIIB 的进入被 SDF-1 阻断。 RANTES 通过 CXCR4 受体与 CCR5 和 SDF-1 相互作用。缺乏功能性 CCR5 受体的个体的 DC 中 M 向性病毒的进入被消除，而 T 向性病毒则没有。 DC 比 T 细胞表达更多的 CCR5 和 CXCR4 mRNA。因此，虽然 HIV-1 在成熟 DC 中不能有效复制，但病毒进入可能是活跃的，并且可以被作用于已知的 M 和 T 向性病毒受体的趋化因子阻断。
HIV-1 actively replicates in dendritic cell (DC)-T cell cocultures, but it has been difficult to demonstrate substantial infection of purified mature DCs. We now find that HIV-1 begins reverse transcription much more efficiently in DCs than T cells, even though T cells have higher levels of CD4 and gp120 binding. DCs isolated from skin or from blood precursors behave similarly. Several M-tropic strains and the T-tropic strain IIIB enter DCs efficiently, as assessed by the progressive formation of the early products of reverse transcription after a 90-min virus pulse at 37°C. However, few late gag-containing sequences are detected, so that active viral replication does not occur. The formation of these early transcripts seems to follow entry of HIV-1, rather than binding of virions that contain viral DNA. Early transcripts are scarce if DCs are exposed to virus on ice for 4 h, or for 90 min at 37°C, conditions which allow virus binding. Also the early transcripts once formed are insensitive to trypsin. The entry of a M-tropic isolates is blocked by the chemokine RANTES, and the entry of IIIB by SDF-1. RANTES interacts with CCR5 and SDF-1 with CXCR4 receptors. Entry of M-tropic but not T-tropic virus is ablated in DCs from individuals who lack a functional CCR5 receptor. DCs express more CCR5 and CXCR4 mRNA than T cells. Therefore, while HIV-1 does not replicate efficiently in mature DCs, viral entry can be active and can be blocked by chemokines that act on known receptors for M- and T-tropic virus.