Brain Institute, Federal University of Rio Grande do Norte, Natal, RN 59078970, Brazil;
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Proc Natl Acad Sci U S A. 2021 May 4;118(18). doi: 10.1073/pnas.2025167118.
The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inconsistent with universal structure conservation and function across vertebrates. Linked to the LDLR functional domain loss, zebra finches show inefficient infectivity by lentiviruses (LVs) pseudotyped with VSV G, which can be rescued by the expression of human LDLR. Finches also show an atypical plasma lipid distribution that relies largely on high-density lipoprotein (HDL). These findings provide insights into the genetics and evolution of viral infectivity and cholesterol transport mechanisms in vertebrates.
低密度脂蛋白受体（LDLR）是细胞摄取胆固醇的关键，也是水疱性口炎病毒糖蛋白（VSV G）的主要受体。在这里，我们表明，在鸣禽中 LDLR 高度多样化，缺乏配体结合和细胞运输所必需的结构域，与普遍的结构保守性和脊椎动物中的功能不一致。与 LDLR 功能域缺失相关的是，斑胸草雀通过假型为 VSV G 的慢病毒（LVs）的感染效率较低，而表达人 LDLR 可以挽救这种情况。雀类还表现出一种非典型的血浆脂质分布，主要依赖于高密度脂蛋白（HDL）。这些发现为我们提供了有关脊椎动物病毒感染性和胆固醇运输机制的遗传学和进化的见解。
