HIV-1 reactivation in resting peripheral blood mononuclear cells of infected adults upon in vitro CD4 cross-linking by ligands of the CDR2-loop in extracellular domain 1
HIV-1 reactivation in resting peripheral blood mononuclear cells of infected adults upon in vitro CD4 cross-linking by ligands of the CDR2-loop in extracellular domain 1
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DOI：
10.1097/00126334-199905010-00002
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发表时间：
1999-05-01
期刊：
影响因子：
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通讯作者：
Devaux, C
中科院分区：
文献类型：
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作者：
Briant, L;Reynes, J;Devaux, C
HIV-1感染静息外周血单个核细胞（PBMCs），但保持失活状态，直到；随后的细胞激活。我们已经证明，gp120-抗gp120免疫复合物或热灭活的HIV-1 （ihhtv -1）与细胞表面CD4的交联足以触发激活信号，导致病毒再激活(9)。在这项研究中，我们证明了NF-KB核易位和iHIV-1对病毒产生的刺激与用作外源刺激的病毒蛋白浓度密切相关。此外，我们进一步研究了这些观察结果的生理学相关性。当iHIV-1向体外CD4交联时，发现来自hiv -1感染患者的pbmc产生病毒。这种病毒再激活与患者外周血单核细胞中NF-KB核易位增加有关。此外，在体外感染HIV-1的静息pbmc中，发现病毒再激活是由CD4（病毒包膜和抗CD4单克隆抗体）结构域1 (D1) cdr2环的配体特异性诱导的。相比之下，结合D1上其他表位（包括D1/ cdr3环）的抗体在CD4低聚化后未观察到病毒再激活。最后，可溶性CD4 （sCD4）阻止D1/ cdr2环配体对病毒的再激活。我们的研究结果表明，在pbmc中，由D1/ cdr2环上CD4的低聚化引发的信号事件可以触发感染个体中HIV-1的上调。
HIV-1 infects resting peripheral blood mononuclear cells (PBMCs) but remains inactive state until;subsequent cell activation. We have demonstrated that the cross-linking of cell surface CD4 by gp120-anti-gp120 immune complexes or heat inactivated HIV-1 ((iHTV-1) is sufficient to trigger activation signals leading to virus reactivation (9). In this study, we demonstrate that NF-KB nuclear translocation and stimulation of virus production by iHIV-1 were strictly linked to the concentrations of viral proteins used as exogenous stimuli. Moreover, we further investigated the physiologic relevance of these observations. When submitted to an in vitro CD4 crosslinking by iHIV-1, PBMCs from HIV-l-infected patients were found to produce virus. This viral reactivation was associated with increased NF-KB nuclear translocation in patients' PBMCs. Additionally, virus reactivation in resting PBMCs infected in vitro with HIV-1 was found to be specifically induced by ligands of the CDR2-loop in domain 1 (D1) of CD4 (virus envelope and anti-CD4 monoclonal antibodies). In contrast, virus reactivation was not observed following CD4 oligomerization by antibodies that bind other epitopes in D1, including the D1/CDR3-loop. Finally, soluble CD4 (sCD4) prevented virus reactivation by D1/CDR2-loop ligands. Our results indicate that the signaling events initiated in PBMCs by oligomerization of CD4 at the D1/CDR2-loop can trigger HIV-1 upregulation in infected individuals.