Virology Research Group, Regional Centre for Biotechnology, NCR Biotech Science Cluster, Faridabad 121001, India.
Biochem Soc Trans. 2023 Aug 31;51(4):1621-1633. doi: 10.1042/BST20221500.
Guanylate-binding proteins (GBPs) are immune GTPases that are induced in response to interferon stimulation/pathogen infection. These proteins arose early in evolution and have multiple physiological roles ranging from tumor suppression to anti-microbial functions. While several studies describe their mechanistic role in the lysis of bacteria/pathogen vacuole, and activation of the inflammasome, their functions in viral infections are only just emerging. The role of the GBPs in virus infections is multifaceted, being both dependent on and independent of GTP binding/hydrolysis and isoprenylation. Diverse antiviral roles are documented such as inhibition of viral RNA/protein synthesis, block of viral envelope glycoprotein processing, and targeting viral protein for degradation. Not surprisingly, several viral proteins bind to specific GBPs and antagonize their antiviral effects. While recruitment of GBP1, Gbp1, Gbp2 on the virus replication complex has been reported, the functional implications of this are not entirely clear. Furthermore, their role in interferon and inflammation activation during virus infection are contradictory, with reports of both positive and negative regulation. Here, we discuss the emerging functional roles of GBPs in virus infections.
鸟苷酸结合蛋白（GBP）是一种免疫 GTPase，可响应干扰素刺激/病原体感染而诱导产生。这些蛋白质在进化早期出现，具有多种生理作用，从肿瘤抑制到抗微生物功能。虽然有几项研究描述了它们在细菌/病原体空泡裂解和炎症小体激活中的作用机制，但它们在病毒感染中的功能才刚刚开始显现。GBP 在病毒感染中的作用是多方面的，既依赖于 GTP 结合/水解和异戊二烯化，又独立于 GTP 结合/水解和异戊二烯化。已经记录了多种抗病毒作用，例如抑制病毒 RNA/蛋白质合成、阻断病毒包膜糖蛋白加工以及靶向病毒蛋白进行降解。毫不奇怪，几种病毒蛋白与特定的 GBP 结合并拮抗其抗病毒作用。虽然已经报道了 GBP1、Gbp1 和 Gbp2 在病毒复制复合物上的募集，但这一作用的功能意义尚不完全清楚。此外，它们在病毒感染期间干扰素和炎症激活中的作用相互矛盾，既有正调控的报道，也有负调控的报道。在这里，我们讨论了 GBP 在病毒感染中的新兴功能作用。
