Laniosz Valerie, Nguyen Kha C, Meneses Patricio I
School of Graduate and Postdoctoral Studies, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064, USA.
J Virol. 2007 Jul;81(14):7435-48. doi: 10.1128/JVI.00571-07. Epub 2007 May 2.
Events that lead to viral infections include the binding of the virus to the target cells, internalization of the virus into the cells, and the ability of the viral genome to be expressed. These steps are mediated by cellular and viral proteins and are temporally regulated. The papillomavirus capsid consists of two virally encoded capsid proteins, L1 and L2. Much is known about the role of the major capsid protein L1 compared to what is known of the role of the L2 protein. We identified the interaction of the L2 protein with SNARE protein syntaxin 18, which mediates the trafficking of vesicles and their cargo between the endoplasmic reticulum, the cis-Golgi compartment, and possibly the plasma membrane. Mutations of L2 residues 41 to 44 prevented the interaction of L2 protein with syntaxin 18 in cotransfection experiments and resulted in noninfectious pseudovirions. In this paper, we describe that syntaxin 18 colocalizes with infectious bovine papillomavirus type 1 (BPV1) pseudovirions during infection but does not colocalize with the noninfectious BPV1 pseudovirions made with an L2 mutant at residues 41 to 44. We show that an antibody against BPV1 L2 residues 36 to 49 (alpha L2 36-49) binds to in vitro-generated BPV1 pseudoviral capsids and does not coimmunoprecipitate syntaxin 18- and BPV1 L2-transfected proteins. alpha L2 36-49 was able to partially or completely neutralize infection of BPV1 pseudovirions and genuine virions. These results support the dependence of syntaxin 18 during BPV1 infection and the ability to interfere with infection by targeting the L2-syntaxin 18 interaction and further define the infectious route of BPV1 mediated by the L2 protein.
导致病毒感染的事件包括病毒与靶细胞的结合、病毒内化进入细胞以及病毒基因组的表达能力。这些步骤由细胞和病毒蛋白介导，并受到时间调控。乳头瘤病毒衣壳由两种病毒编码的衣壳蛋白L1和L2组成。与L2蛋白的作用相比，人们对主要衣壳蛋白L1的作用了解更多。我们鉴定了L2蛋白与SNARE蛋白 syntaxin 18的相互作用，syntaxin 18介导囊泡及其货物在内质网、顺式高尔基体区室以及可能的质膜之间的运输。在共转染实验中，L2蛋白41至44位残基的突变阻止了L2蛋白与syntaxin 18的相互作用，并导致无感染性的假病毒颗粒。在本文中，我们描述了在感染过程中，syntaxin 18与感染性牛乳头瘤病毒1型（BPV1）假病毒颗粒共定位，但不与由41至44位残基处L2突变体制备的无感染性BPV1假病毒颗粒共定位。我们表明，针对BPV1 L2蛋白36至49位残基的抗体（αL2 36 - 49）与体外产生的BPV1假病毒衣壳结合，并且不会与syntaxin 18和BPV1 L2转染蛋白进行共免疫沉淀。αL2 36 - 49能够部分或完全中和BPV1假病毒颗粒和真正病毒颗粒的感染。这些结果支持了syntaxin 18在BPV1感染过程中的依赖性，以及通过靶向L2 - syntaxin 18相互作用来干扰感染的能力，并进一步确定了由L2蛋白介导的BPV1的感染途径。
