Department of Veterinary Public Health, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
PLoS One. 2013;8(2):e55920. doi: 10.1371/journal.pone.0055920. Epub 2013 Feb 6.
Human guanylate-binding protein 1 (hGBP1) is an interferon-inducible protein involved in the host immune response against viral infection. In response to infection by influenza A virus (IAV), hGBP1 transcript and protein were significantly upregulated. Overexpression of hGBP1 inhibited IAV replication in a dose-dependent manner in vitro. The lysine residue at position 51 (K51) of hGBP1 was essential for inhibition of IAV replication. Mutation of K51 resulted in an hGBP1 that was unable to inhibit IAV replication. The viral nonstructural protein 1 (NS1) was found to interact directly with hGBP1. K51 of hGBP1 and a region between residues 123 and 144 in NS1 were demonstrated to be essential for the interaction between NS1 and hGBP1. Binding of NS1 to hGBP1 resulted in a significant reduction in both GTPase activity and the anti-IAV activity of hGBP1. These findings indicated that hGBP1 contributed to the host immune response against IAV replication and that hGBP1-mediated antiviral activity was antagonized by NS1 via binding to hGBP1.
人鸟苷酸结合蛋白 1(hGBP1)是一种干扰素诱导的蛋白,参与宿主对病毒感染的免疫反应。在甲型流感病毒(IAV)感染时,hGBP1 的转录本和蛋白水平显著上调。体外实验中,hGBP1 的过表达以剂量依赖性方式抑制 IAV 复制。hGBP1 第 51 位赖氨酸残基(K51)对于抑制 IAV 复制是必需的。K51 突变导致 hGBP1 无法抑制 IAV 复制。发现病毒非结构蛋白 1(NS1)与 hGBP1 直接相互作用。hGBP1 的 K51 残基和 NS1 中 123 到 144 位残基之间的区域对于 NS1 和 hGBP1 之间的相互作用是必需的。NS1 与 hGBP1 的结合导致 hGBP1 的 GTPase 活性和抗 IAV 活性显著降低。这些发现表明,hGBP1 有助于宿主对 IAV 复制的免疫反应,并且 NS1 通过与 hGBP1 结合拮抗 hGBP1 介导的抗病毒活性。