title: Human immunodeficiency virus (HIV) type 1 Vpu induces the expression of CD40 in endothelial cells and regulates HIV-induced adhesion of B-lymphoma cells.
abstract: 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239, USA.
authors.forename: Winnie W
authors.initials: WW
authors.lastname: Henderson
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ruhl
authors.forename: Paul
authors.initials: P
authors.lastname: Lewis
authors.forename: Matthew
authors.initials: M
authors.lastname: Bentley
authors.forename: Jay A
authors.initials: JA
authors.lastname: Nelson
authors.forename: Ashlee V
authors.initials: AV
authors.lastname: Moses
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology* / Q000821:virology; D004730:Endothelium, Vascular / Q000166:cytology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D019013:CD40 Antigens; D054298:Human Immunodeficiency Virus Proteins; D019010:Vascular Cell Adhesion Molecule-1; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins