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

Abstract

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. IMPORTANCEBased 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.

Impairing the function of MLCK, myosin Va or myosin Vb disrupts Rhinovirus B14 replication

“…Internalization of RV-A2 and RV-B14 were reduced in cells expressing dominant-negative dynamin II (K44A) 24 – 27 probably due to disturbance of proper clathrin-coated pit maturation 28 . Regardless of actin dependence of RVs 9 , 29 , RV-A2, RV-A16, RV-B3, and RV-B14 infections were not impaired in nocodazole treated cells 8 , 18 , 21 , 30 . Nonetheless, RV-B89 infection seems to be different, as ciliobrevin and nocodazole can reduce infection 8 , 9 .…”

“…Regardless of actin dependence of RVs 9 , 29 , RV-A2, RV-A16, RV-B3, and RV-B14 infections were not impaired in nocodazole treated cells 8 , 18 , 21 , 30 . Nonetheless, RV-B89 infection seems to be different, as ciliobrevin and nocodazole can reduce infection 8 , 9 .…”

“…Conzemius et al . demonstrated that RV-B14 infection progressed in cells expressing a dominant-negative Rab11 8 . This demonstrated that RV-B14 does not enter the endosome recycling pathway.…”

“…Rhinovirus infection strongly depends on cytoskeletal proteins 9 . Overexpression of the Rab11 mutants Rab11-GTP (constitutively active) and Rab11-GDP (a dominant-negative) revealed that uncoating of RV-A89 depends on Rab11 8 . Other Rab11 dependent viruses include type I parainfluenza virus 58 , respiratory syncytial virus 41 , and human immunodeficiency virus 1, which are also dependent on myosin Vb during infection 59 .…”

Meningitic Escherichia coli-induced upregulation of PDGF-B and ICAM-1 aggravates blood-brain barrier disruption and neuroinflammatory response

“…ICAM-1 is now widely considered to be an important marker for endothelium activation, and its canonical function is widely believed to promote migration of leukocytes or monocytes to the infection site [21]. ICAM-1 is reported to be highly induced in response to a variety of pathogenic microbes, such as Plasmodium falciparum [22] and E. coli [23], and has been identified as a receptor for virus infection, such as rhinoviruses [24]. In a previous study of transcriptomics data, we found that ICAM-1 was significantly increased in hBMECs upon meningitic E. coli infection [18], indicating activation of BMECs.…”