Kaposi’s Sarcoma-Associated Virus Governs Gene Expression Profiles Toward B Cell Transformation

Abstract

Kaposi’s sarcoma-associated herpesvirus (KSHV), also called human herpesvirus-8 (HHV-8) was found in patients’ specimens as a causative agent of Kaposi’s sarcoma by representational difference analysis (RDA) (Chang et al., 1994). Initially identified fragments by RDA were KS330Bam and KS631Bam, which showed a sequence similarity to a portion of the open reading frame (ORF) 26 open reading frame encoding the capsid protein VP23 of herpesvirus saimiri (HVS) and the amino acid sequence encoded by the corresponding BDLF1 ORF of Epstein-Barr virus (EBV), and to the tegment protein, ORF75 and also the tegment protein of EBV, BNRF1 (p140), respectively. The following full sequence analysis revealed that KSHV was belonging to the -herpesvirus subfamily, the genus rhadinovirus rather than lymphocryptic virus and could be a new oncogenic DNA virus (Moore et al., 1996; Russo et al., 1996). KSHV is supposed to infect various kinds of tissue in vitro at least by using integrin V as a receptor (Garrigues et al., 2008) and establishes latency in B cells (Chen and Lagunoff, 2005). KSHV has been reported to infect a primary endothelial cell and can transform it into a spindle cell which is a characteristic feature of the oncogenic activity of KSHV in endothelial cells (Lagunoff et al., 2002) However, it has not been revealed effective in vitro infection to primary peripheral blood mononuclear cells (PBMC), which of course include B cell, as EBV can form lymphoblastoid cell lines (LCL). Extensive studies so far have revealed that KSHV should be an etiologic agent for Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL) (Hengge et al., 2002a; Hengge et al., 2002b). It is quite a big question how oncogenic viruses are involved in their related cancers. Especially limited host ranges of viruses only infecting with humans make this question more unanswerable. One approach to get a hint about this question and solve it is to see gene expression profiles of viruses-associated tumors. Recently, we analyzed three types of typical lymphocyte-originated tumor cell lines-primary effusion lymphoma (PEL) cell lines,