7th Conference on Retroviruses and Opportunistic Infections San Francisco, CA - January 30 -February 4, 2000

Conf Retroviruses Opportunistic Infect 2000 Jan 30-Feb 2; 7:75 (abstract no. 4)

D. Bose¹, S. Pati¹, N. Liu¹, M. Reitz¹, And F. Samaniego^2
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 NFκB-dependent transcription. U937 cells transfected with K1 show increased binding of NFκB 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.

Keywords: AEGIS, Herpesvirus 8, Human, Open Reading Frames, Sarcoma, Kaposi, Cell Physiology, COS Cells, Signal Transduction, Tyrosine, Cytokines, Lymphoma, Transcription, Genetic, Protein-Tyrosine Kinase, Animal, Human, Mice, genetics, AIDS

2000-01-30
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