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Human Herpesvirus 8 Open Reading Frame K1 Signals through NFkB and Activates Cells D. BOSE*1, S. PATI1, N. LIU1, M. REITZ1, and F. SAMANIEGO2. 1Inst. of Human Virology and 2Greenebaum Cancer Ctr., Univ. of Maryland, Baltimore Human herpesvirus 8 (HHV8) is associated with the development of Kaposi's sarcoma (KS), multicentric Castleman's disease (MCD), and body cavity-based lymphoma (BCBL). We PCR-cloned open reading frame K1 of the HHV8 genome in order to investigate its role in HHV8-associated disease. K1 is a transmembrane protein with an intracellular immunoreceptor tyrosine-based activation motif (ITAM) and an extracellular immunoglobulin l light chain-like domain. K1 expressed in COS-1 cells exists as a multimeric complex and is constitutively phosphorylated. Cells transfected with K1 showed activation of NFkB-dependent transcription. U937 cells transfected with K1 show increased binding of NFkB DNA response elements as well as enhanced chemotaxis to monocyte chemotactic protein 2 (MCP2). Naive U937 cells also show enhanced chemotaxis to media conditioned by K1 transfectants. K1 transfected endothelial KS cells produce increased amounts of GM-CSF and other cytokines. K1 transgenic mice produced by oocyte injection show dysregulated cell proliferation in response to PMA stimulation. Taken together the results presented here demonstrate that K1 expression produces cellular activation that leads to enhanced production of cytokines and changes in biological function that are consistent with a pro-inflammatory role for K1. As inflammation has been identified as a critical aspect of KS pathology, our results demonstrate that HHV8 may play a role in promoting inflammation in KS through K1 expression. Key Words: human herpesvirus 8, inflammation, Kaposi's sarcoma |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |