Conzemius Rick, Ganjian Haleh, Blaas Dieter, Fuchs Renate
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Vienna, Austria.
Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
J Virol. 2016 Aug 12;90(17):7934-42. doi: 10.1128/JVI.00712-16. Print 2016 Sep 1.
Human rhinovirus A89 (HRV-A89) and HRV-B14 bind to and are internalized by intercellular adhesion molecule 1 (ICAM-1); as demonstrated earlier, the RNA genome of HRV-B14 penetrates into the cytoplasm from endosomal compartments of the lysosomal pathway. Here, we show by immunofluorescence microscopy that HRV-A89 but not HRV-B14 colocalizes with transferrin in the endocytic recycling compartment (ERC). Applying drugs differentially interfering with endosomal recycling and with the pathway to lysosomes, we demonstrate that these two major-group HRVs productively uncoat in distinct endosomal compartments. Overexpression of constitutively active (Rab11-GTP) and dominant negative (Rab11-GDP) mutants revealed that uncoating of HRV-A89 depends on functional Rab11. Thus, two ICAM-1 binding HRVs are routed into distinct endosomal compartments for productive uncoating.
Based on similarity of their RNA genomic sequences, the more than 150 currently known common cold virus serotypes were classified as species A, B, and C. The majority of HRV-A viruses and all HRV-B viruses use ICAM-1 for cell attachment and entry. Our results highlight important differences of two ICAM-1 binding HRVs with respect to their intracellular trafficking and productive uncoating; they demonstrate that serotypes belonging to species A and B, but entering the cell via the same receptors, direct the endocytosis machinery to ferry them along distinct pathways toward different endocytic compartments for uncoating.
人鼻病毒A89（HRV - A89）和HRV - B14可与细胞间黏附分子1（ICAM - 1）结合并被其内化；如先前所示，HRV - B14的RNA基因组可从溶酶体途径的内体区室进入细胞质。在此，我们通过免疫荧光显微镜观察发现，HRV - A89而非HRV - B14与转铁蛋白在内吞再循环区室（ERC）中共定位。应用不同地干扰内体再循环和溶酶体途径的药物，我们证明这两种主要组别的鼻病毒在不同的内体区室中有效地脱壳。组成型活性（Rab11 - GTP）和显性负性（Rab11 - GDP）突变体的过表达表明，HRV - A89的脱壳依赖于功能性Rab11。因此，两种与ICAM - 1结合的鼻病毒被导向不同的内体区室以进行有效的脱壳。
基于其RNA基因组序列的相似性，目前已知的150多种普通感冒病毒血清型被分类为A、B和C种。大多数HRV - A病毒和所有HRV - B病毒利用ICAM - 1进行细胞附着和进入。我们的结果突出了两种与ICAM - 1结合的鼻病毒在细胞内运输和有效脱壳方面的重要差异；它们表明属于A种和B种但通过相同受体进入细胞的血清型，指导内吞机制将它们沿着不同途径转运至不同的内吞区室进行脱壳。
