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Journal of Virology, August 2004, p. 8146-8158, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8146-8158.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Role of Nucleolin in Human Parainfluenza Virus Type 3 Infection of Human Lung Epithelial Cells

Santanu Bose, Mausumi Basu, and Amiya K. Banerjee*

Department of Virology, The Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195

Received 28 October 2003/ Accepted 15 March 2004

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.

* Corresponding author. Mailing address: Department of Virology, LRI/Room NN-10, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195. Phone: (216) 444-0625. Fax: (216) 444-2998. E-mail: banerja{at}ccf.org.

Journal of Virology, August 2004, p. 8146-8158, Vol. 78, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.15.8146-8158.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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