Biswas P, Mantelli B, Delfanti F, Cota M, Vallanti G, Mengozzi M, Vicenzi E, Lazzarin A, Poli G
Laboaratory of Clinical Immunology, Scientific Institute H San Raffaele, Milan, Italy.
Cytokine. 2001 Jan 7;13(1):55-59. doi: 10.1006/cyto.2000.0798.
U937 cell clones in which efficient (plus) vs poor (minus) replication of HIV-1 occurs have been described. We evaluated the role of host factors in their differential ability to support HIV-1 replication. Plus clones constitutively produced TNF-alpha and viral replication was inhibited by neutralization of endogenous TNF-alpha. However, HIV-1 replication was strongly upregulated in minus clones by exogenous TNF-alpha, which also further accelerated the kinetics of infection in plus clones. We observed an increased accumulation of proviral DNA within one round of HIV-1 replication following TNF-a treatment of plus cells. This effect was associated with increased surface density of CXCR4 in both plus and minus clones. Our results identify TNF-alpha as one correlate that contributes to the higher ability of U937-plus clones to sustain HIV-1 replication. Furthermore, we suggest that TNF-alpha may affect steps of the viral life cycle that occur earlier than transcription and also enhance HIV-1 replication by increasing the surface density of CXCR4.
已有研究报道了U937细胞克隆，其中HIV-1能够高效（阳性）或低效（阴性）复制。我们评估了宿主因子在其支持HIV-1复制的不同能力中的作用。阳性克隆组成性地产生肿瘤坏死因子-α（TNF-α），内源性TNF-α的中和作用可抑制病毒复制。然而，外源性TNF-α可使阴性克隆中的HIV-1复制强烈上调，这也进一步加速了阳性克隆中的感染动力学。在对阳性细胞进行TNF-α处理后，我们观察到在一轮HIV-1复制过程中前病毒DNA的积累增加。这种效应与阳性和阴性克隆中CXCR4表面密度的增加有关。我们的结果确定TNF-α是导致U937阳性克隆维持HIV-1复制能力更强的一个相关因素。此外，我们认为TNF-α可能影响病毒生命周期中早于转录发生的步骤，并且还通过增加CXCR4的表面密度来增强HIV-1复制。
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