ICAM-1 Binding Rhinoviruses A89 and B14 Uncoat in Different Endosomal Compartments

• Published in: Journal of virology Vol. 90; no. 17; pp. 7934 - 7942
• Main Authors: Conzemius, Rick, Ganjian, Haleh, Blaas, Dieter, Fuchs, Renate
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.09.2016
• Subjects: Endosomes - virology; HeLa Cells; Human rhinovirus; Humans; Intercellular Adhesion Molecule-1 - metabolism; Medicin och hälsovetenskap; Microscopy, Fluorescence; rab GTP-Binding Proteins - metabolism; Rhinovirus - physiology; Virus Attachment; Virus Uncoating; Virus-Cell Interactions
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/JVI.00712-16

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.