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Journal of Virology, May 2004, p. 4408-4420, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4408-4420.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus (HIV) Type 1 Vpu Induces the Expression of CD40 in Endothelial Cells and Regulates HIV-Induced Adhesion of B-Lymphoma Cells

Winnie W. Henderson,1 Rebecca Ruhl,2 Paul Lewis,3 Matthew Bentley,2 Jay A. Nelson,1 and Ashlee V. Moses1,2*

Department of Molecular Microbiology and Immunology,1 Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239,2 Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon 970063

Received 21 August 2003/ Accepted 8 January 2004

AIDS-related B-cell non-Hodgkin's lymphoma (AIDS-NHL) is a significant cause of morbidity and mortality among individuals infected with human immunodeficiency virus type 1 (HIV-1). AIDS-NHL is clinically and histologically heterogeneous, but common features include an aggressive clinical course and frequent extranodal presentation. HIV-1 infection of nonimmune cells that interact with malignant B cells at extranodal sites may influence both the development and the clinical presentation of disease. Our previous studies have shown that coculture of B-lymphoma (BL) cells with HIV-1-infected endothelial cells (EC) leads to contact activation of EC and firm BL-cell adhesion. The key event promoting EC-BL-cell adhesion was HIV-1 upregulation of endothelial CD40, which allowed induction of vascular cell adhesion molecule 1 (VCAM-1) in a CD40-dependent manner. The present study was designed to identify the HIV-1 protein(s) that influence EC-BL-cell adhesion. When HIV-1 proteins were individually expressed in EC by using recombinant adenoviruses, cultured BL cells adhered exclusively to Vpu-transduced EC. As with HIV-infected EC, adhesive properties were linked to the capacity of Vpu to upregulate CD40, which in turn allowed efficient expression of VCAM-1. When EC were infected with an HIV-1 pseudotype lacking the Vpu gene, CD40 upregulation and BL-cell adhesive properties were lost, indicating an essential role for Vpu in EC-BL-cell interactions. Thus, these data reveal a novel function for HIV-1 Vpu and further suggest a role for Vpu in the development of AIDS-NHL at EC-rich extranodal sites.

* Corresponding author. Mailing address: Vaccine and Gene Therapy Institute, 505 NW 185th Ave., Beaverton, OR 97006. Phone: (503) 418-2712. Fax: (503) 418-2701. E-mail: mosesa{at}ohsu.edu.

Journal of Virology, May 2004, p. 4408-4420, Vol. 78, No. 9
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.9.4408-4420.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Smith, J R, Henderson, W W, Rosenbaum, J T, Neuwelt, E A, Moses, A V (2008). Cultured human endothelial cells expressing HIV-1 Vpu and Tat support the expansion of malignant B cells from primary central nervous system lymphoma. Br J Ophthalmol 92: 297-299 [Full Text]  


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