Role of nucleolin in human parainfluenza virus type 3 infection of human lung epithelial cells.
Human parainfluenza virus type 3 (HPIV-3) is an airborne pathogen that infects human lung epithelial cells from the apical (luminal) plasma membrane domain. In the present study, we have identified cell surface-expressed nucleolin as a cellular cofactor required for the efficient cellular entry of HPIV-3 into human lung epithelial A549 cells. Nucleolin was enriched on the apical cell surface domain of A549 cells, and HPIV-3 interacted with nucleolin during entry. The importance of nucleolin during HPIV-3 replication was borne out by the observation that HPIV-3 replication was significantly inhibited following (i). pretreatment of cells with antinucleolin antibodies and (ii). preincubation of HPIV-3 with purified nucleolin prior to its addition to the cells. Moreover, HPIV-3 cellular internalization and attachment assays performed in the presence of antinucleolin antibodies and purified nucleolin revealed the requirement of nucleolin during HPIV-3 internalization but not during attachment. Thus, these results suggest that nucleolin expressed on the surfaces of human lung epithelial A549 cells plays an important role during HPIV-3 cellular entry.
Bose
Santanu
S
Department of Virology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Basu
Mausumi
M
Banerjee
Amiya K
AK
D004847:Epithelial Cells / Q000821:virology; D015707:HN Protein / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000821:virology*; D010224:Parainfluenza Virus 3, Human / Q000502:physiology*; D010750:Phosphoproteins / Q000032:analysis / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000378:metabolism; D014779:Virus Replication; D000097796:Nucleolin
D015707:HN Protein; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D014760:Viral Fusion Proteins; D000097796:Nucleolin