Dipartimento di Biologia, Università degli Studi di Roma "Tor Vergata", Roma, Italy.
Dipartimento di Medicina Sperimentale, Università degli Studi di Roma "Tor Vergata", Roma, Italy.
Front Immunol. 2022 May 19;13:830788. doi: 10.3389/fimmu.2022.830788. eCollection 2022.
A strategy adopted to combat human immunodeficiency virus type-1 (HIV-1) infection is based on interfering with virus entry into target cells. In this study, we found that phosphatidylcholine (PC) liposomes reduced the expression of the CD4 receptor in human primary type-1 macrophages but not in CD4 T cells. The down-regulation was specific to CD4, as any effect was not observed in CCR5 membrane expression. Moreover, the reduction of membrane CD4 expression required the Ca-independent protein kinase C (PKC), which in turn mediated serine phosphorylation in the intracytoplasmic tail of the CD4 receptor. Serine phosphorylation of CD4 was also associated with its internalization and degradation in acidic compartments. Finally, the observed CD4 downregulation induced by PC liposomes in human primary macrophages reduced the entry of both single-cycle replication and replication competent R5 tropic HIV-1. Altogether, these results show that PC liposomes reduce HIV entry in human macrophages and may impact HIV pathogenesis by lowering the viral reservoir.
一种用于对抗人类免疫缺陷病毒 1 型（HIV-1）感染的策略是基于干扰病毒进入靶细胞。在这项研究中，我们发现磷脂酰胆碱（PC）脂质体降低了人类原发性 1 型巨噬细胞中 CD4 受体的表达，但对 CD4 T 细胞没有影响。下调是特异性的 CD4，因为在 CCR5 膜表达中没有观察到任何影响。此外，膜 CD4 表达的减少需要钙非依赖性蛋白激酶 C（PKC），它反过来介导 CD4 受体胞质尾内丝氨酸磷酸化。CD4 的丝氨酸磷酸化也与其在酸性隔室中的内化和降解有关。最后，PC 脂质体在人原代巨噬细胞中观察到的 CD4 下调降低了单周期复制和有复制能力的 R5 嗜性 HIV-1 的进入。总的来说，这些结果表明 PC 脂质体降低了人类巨噬细胞中 HIV 的进入，通过降低病毒储存库可能影响 HIV 的发病机制。
