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Journal of Virology, November 2004, p. 12647-12656, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12647-12656.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Serotype-Specific Entry of Dengue Virus into Liver Cells: Identification of the 37-Kilodalton/67-Kilodalton High-Affinity Laminin Receptor as a Dengue Virus Serotype 1 Receptor

Chutima Thepparit and Duncan R. Smith*

Institute of Molecular Biology and Genetics, Mahidol University, Thailand

Received 3 April 2004/ Accepted 29 June 2004

Dengue virus, the causative agent of dengue fever, dengue shock syndrome, and dengue hemorrhagic fever, infects susceptible cells by initially binding to a receptor(s) located on the host cell surface. Evidence to date suggests that receptor usage may be cell and serotype specific, and this study sought to identify dengue virus serotype 1 binding proteins on the surface of liver cells, a known target organ. By using a virus overlay protein binding assay (VOPBA), in both nondenaturing and denaturing gel systems, a putative dengue virus serotype 1 binding protein of approximately 37 kDa expressed on the surface of liver (HepG2) cells was identified. Mass spectrometry analysis identified a candidate protein, the 37/67-kDa high-affinity laminin receptor. Entry of the dengue virus serotype 1 was significantly inhibited in a dose-dependent manner by both antibodies directed against the 37/67-kDa high-affinity laminin receptor and soluble laminin. No inhibition of virus entry was seen with dengue virus serotypes 2, 3, or 4, demonstrating that the 37/67-kDa high-affinity laminin receptor is a serotype-specific receptor for dengue virus entry into liver cells.

* Corresponding author. Mailing address: Molecular Pathology Laboratory, Institute of Molecular Biology and Genetics, Mahidol University, 25/25 Phuttamontol Sai 4, Salaya, Nakorn Pathom, Thailand 73170. Phone: 662 800 3624. Fax: 662 441 9906. E-mail: duncan_r_smith{at}hotmail.com.

Journal of Virology, November 2004, p. 12647-12656, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12647-12656.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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