Human immunodeficiency virus type 1 replication in dendritic cell-T-cell cocultures is increased upon incorporation of host LFA-1 due to higher levels of virus production in immature dendritic cells
Human immunodeficiency virus type 1 replication in dendritic cell-T-cell cocultures is increased upon incorporation of host LFA-1 due to higher levels of virus production in immature dendritic cells
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DOI：
10.1128/jvi.02810-06
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Tremblay, Michel J.
中科院分区：
文献类型：
--
作者：
Gilbert, Caroline;Cantin, Rejean;Tremblay, Michel J.
树突状细胞（Dendritic cells，DCs）是人类免疫缺陷病毒1型（human immunodeficiency virus type-1，HIV-1）侵袭的重要细胞。在这里，我们研究了是否病毒粒子纳入宿主细胞膜蛋白可以影响DC-T细胞共培养物中的病毒复制。使用无或承载宿主来源的白细胞功能相关抗原1（LFA-1）的同基因病毒，我们表明，HIV-1的生产增加时，LFA-1轴承病毒粒子相比，缺乏这种粘附分子的病毒实体使用。这种现象仅在未成熟单核细胞衍生的DC（IM-MDDC）中观察到，而在显示成熟表型的DC中未观察到。这种增加不是由于应答者CD 4 + T细胞中更高的病毒产生，而是与IM-MDDC的更重要的生产性感染有关。我们提供的证据表明，病毒相关的宿主LFA-1分子不影响HFV-1生命周期中的晚期事件，而是对病毒复制的早期步骤产生影响。我们证明了由病毒锚定的宿主LFA-1赋予的IM-MDDC的生产性感染的增强涉及蛋白激酶A（PKA）和PKC信号转导途径。通过用原代人细胞中产生的病毒原液和抗LFA-1抗体进行实验，确定了该现象的生物学意义。总之，我们的研究结果表明，一些病毒结合的宿主蛋白质和它们的天然同源配体之间的关联可以调节IM-MDDC的从头HfV-1产生。因此，病毒结合的宿主细胞膜成分和DC表面上的反受体之间的额外相互作用可以影响IM-MDDC-T细胞共培养物中的HIV-1复制。
Dendritic cells (DCs) act as a portal for invasion by human immunodeficiency virus type-1 (HIV-1). Here, we investigated whether virion-incorporated host cell membrane proteins can affect virus replication in DC-T-cell cocultures. Using isogenic viruses either devoid of or bearing host-derived leukocyte function-associated antigen 1 (LFA-1), we showed that HIV-1 production is augmented when LFA-1-bearing virions are used compared to that for viral entities lacking this adhesion molecule. This phenomenon was observed in immature monocyte-derived DCs (IM-MDDCs) only and not in DCs displaying a mature phenotype. The increase is not due to higher virus production in responder CD4+ T cells but rather is linked with a more important productive infection of IM-MDDCs. We provided evidence that virus-associated host LFA-1 molecules do not affect a late event in the HfV-1 life cycle but rather exert an effect on an early step in virus replication. We demonstrated that the enhancement of productive infection of IM-MDDCs that is conferred by virus-anchored host LFA-1 involves the protein kinase A (PKA) and PKC signal transduction pathways. The biological significance of this phenomenon was established by performing experiments with virus stocks produced in primary human cells and anti-LFA-1 antibodies. Together, our results indicate that the association between some virus-bound host proteins and their natural cognate ligands can modulate de novo HfV-1 production by IM-MDDCs. Therefore, the additional interactions between virus-bound host cell membrane constituents and counter receptors on the surfaces of DCs can influence HIV-1 replication in IM-MDDC-T-cell cocultures.