Cseke Gabriella, Maginnis Melissa S, Cox Reagan G, Tollefson Sharon J, Podsiad Amy B, Wright David W, Dermody Terence S, Williams John V
Department of Chemistry, Vanderbilt University College of Arts and Sciences, Nashville, TN 37232, USA.
Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1566-71. doi: 10.1073/pnas.0801433106. Epub 2009 Jan 21.
Human metapneumovirus (hMPV) is a recently described paramyxovirus that causes lower respiratory infections in children and adults worldwide. The hMPV fusion (F) protein is a membrane-anchored glycoprotein and major protective antigen. All hMPV F protein sequences determined to date contain an Arg-Gly-Asp (RGD) sequence, suggesting that F engages RGD-binding integrins to mediate cell entry. The divalent cation chelator EDTA, which disrupts heterodimeric integrin interactions, inhibits infectivity of hMPV but not the closely related respiratory syncytial virus (RSV), which lacks an RGD motif. Function-blocking antibodies specific for alphavbeta1 integrin inhibit infectivity of hMPV but not RSV. Transfection of nonpermissive cells with alphav or beta1 cDNAs confers hMPV infectivity, whereas reduction of alphav and beta1 integrin expression by siRNA inhibits hMPV infection. Recombinant hMPV F protein binds to cells, whereas Arg-Gly-Glu (RGE)-mutant F protein does not. These data suggest that alphavbeta1 integrin is a functional receptor for hMPV.
人偏肺病毒（hMPV）是一种最近被发现的副粘病毒，可在全球范围内导致儿童和成人发生下呼吸道感染。hMPV融合（F）蛋白是一种膜锚定糖蛋白，也是主要的保护性抗原。迄今为止确定的所有hMPV F蛋白序列均包含一个精氨酸-甘氨酸-天冬氨酸（RGD）序列，这表明F蛋白通过与RGD结合整合素相互作用来介导细胞进入。二价阳离子螯合剂EDTA可破坏异二聚体整合素相互作用，它能抑制hMPV的感染性，但对缺乏RGD基序的密切相关的呼吸道合胞病毒（RSV）则无抑制作用。针对αvβ1整合素的功能阻断抗体可抑制hMPV的感染性，但对RSV无效。用αv或β1 cDNA转染非允许细胞可赋予hMPV感染性，而通过小干扰RNA（siRNA）降低αv和β1整合素的表达则可抑制hMPV感染。重组hMPV F蛋白可与细胞结合，而精氨酸-甘氨酸-谷氨酸（RGE）突变的F蛋白则不能。这些数据表明αvβ1整合素是hMPV的功能性受体。
