Center for Cancer Research, National Cancer Institute, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
J Virol. 2013 Mar;87(6):3561-70. doi: 10.1128/JVI.03299-12. Epub 2013 Jan 16.
Incorporation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins into assembling particles is crucial for virion infectivity. Genetic and biochemical data indicate that the matrix (MA) domain of Gag and the cytoplasmic tail of the transmembrane glycoprotein gp41 play an important role in coordinating Env incorporation; however, the molecular mechanism and possible role of host factors in this process remain to be defined. Recent studies suggested that Env incorporation is mediated by interactions between matrix and tail-interacting protein of 47 kDa (TIP47; also known as perilipin-3 and mannose-6-phosphate receptor-binding protein 1), a member of the perilipin, adipophilin, TIP47 (PAT) family of proteins implicated in protein sorting and lipid droplet biogenesis. We have confirmed by nuclear magnetic resonance spectroscopy titration experiments and surface plasmon resonance that MA binds TIP47. We also reevaluated the role of TIP47 in HIV-1 Env incorporation in HeLa cells and in the Jurkat T-cell line. In HeLa cells, TIP47 overexpression or RNA interference (RNAi)-mediated depletion had no significant effect on HIV-1 Env incorporation, virus release, or particle infectivity. Similarly, depletion of TIP47 in Jurkat cells did not impair HIV-1 Env incorporation, virus release, infectivity, or replication. Our results thus do not support a role for TIP47 in HIV-1 Env incorporation or virion infectivity.
将人类免疫缺陷病毒 1 型 (HIV-1) 的包膜糖蛋白整合到组装颗粒中对于病毒粒子的感染力至关重要。遗传和生化数据表明，Gag 的基质 (MA) 结构域和跨膜糖蛋白 gp41 的细胞质尾巴在协调 Env 整合中发挥重要作用；然而，宿主因子在这一过程中的分子机制和可能作用仍有待确定。最近的研究表明，Env 整合是由基质与 47kDa 的基质-尾相互作用蛋白（TIP47；也称为 perilipin-3 和甘露糖-6-磷酸受体结合蛋白 1）之间的相互作用介导的，TIP47 是 perilipin、脂肪素、TIP47（PAT）家族蛋白的成员，该家族蛋白参与蛋白质分选和脂滴生物发生。我们通过核磁共振光谱滴定实验和表面等离子体共振证实了 MA 与 TIP47 结合。我们还重新评估了 TIP47 在 HeLa 细胞和 Jurkat T 细胞系中 HIV-1 Env 整合中的作用。在 HeLa 细胞中，TIP47 的过表达或 RNA 干扰（RNAi）介导的耗竭对 HIV-1 Env 整合、病毒释放或粒子感染力没有显著影响。同样，Jurkat 细胞中 TIP47 的耗竭也不会损害 HIV-1 Env 整合、病毒释放、感染力或复制。因此，我们的结果不支持 TIP47 在 HIV-1 Env 整合或病毒粒子感染力中的作用。
