Abstract

HHV-8 has been associated with all forms of Kaposi's sarcoma as well as other lymphoproliferative diseases. The mechanisms of disease development or progression are unknown, but it has been proposed the HHV-8 encoded cytokines may play an important role in the growth of KS and myeloma cells. This application will investigate the role of HHV-8 encoded IL-6 and three B-chemokine homologues (MIP-1a, b, BCK) as mitogenic stimuli for the proliferation of KS and myeloma cells. This investigation will be accomplished by: (1) determining the pattern of expression of vIL-6 and vchemokines in KS cells and in-vitro passaged BCBL cells, (2) comparing the functional activities of the viral and cellular IL-6 and chemokines, (3) defining aspects of the signal transduction pathways of the viral IL-6 and chemokines, and (4) studying the in-vivo effects of vIL-6 and chemokines in a related murine herpesvirus by the use of recombinant viruses. Together these combined analyses will provide data to determine the functional profiles of the viral cytokines and their likely clinical relevance as mediators of HHV-8 associated malignancies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA076445-04
Application #
6489123
Study Section
Virology Study Section (VR)
Program Officer
Read-Connole, Elizabeth Lee
Project Start
1999-01-15
Project End
2003-12-31
Budget Start
2002-01-01
Budget End
2003-12-31
Support Year
4
Fiscal Year
2002
Total Cost
$295,159
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Chen, Daming; Xiang, Qiwang; Nicholas, John (2017) Human Herpesvirus 8 Interleukin-6 Interacts with Calnexin Cycle Components and Promotes Protein Folding. J Virol 91:
Chen, Daming; Nicholas, John (2015) Promotion of Endoplasmic Reticulum-Associated Degradation of Procathepsin D by Human Herpesvirus 8-Encoded Viral Interleukin-6. J Virol 89:7979-90
Cousins, Emily; Gao, Yang; Sandford, Gordon et al. (2014) Human herpesvirus 8 viral interleukin-6 signaling through gp130 promotes virus replication in primary effusion lymphoma and endothelial cells. J Virol 88:12167-72
Cousins, Emily; Nicholas, John (2014) Molecular biology of human herpesvirus 8: novel functions and virus-host interactions implicated in viral pathogenesis and replication. Recent Results Cancer Res 193:227-68
Chen, Daming; Gao, Yang; Nicholas, John (2014) Human herpesvirus 8 interleukin-6 contributes to primary effusion lymphoma cell viability via suppression of proapoptotic cathepsin D, a cointeraction partner of vitamin K epoxide reductase complex subunit 1 variant 2. J Virol 88:1025-38
Cousins, Emily; Nicholas, John (2013) Role of human herpesvirus 8 interleukin-6-activated gp130 signal transducer in primary effusion lymphoma cell growth and viability. J Virol 87:10816-27
Chen, Daming; Cousins, Emily; Sandford, Gordon et al. (2012) Human herpesvirus 8 viral interleukin-6 interacts with splice variant 2 of vitamin K epoxide reductase complex subunit 1. J Virol 86:1577-88
Nicholas, John (2010) Human herpesvirus 8-encoded cytokines. Future Virol 5:197-206
Chen, Daming; Sandford, Gordon; Nicholas, John (2009) Intracellular signaling mechanisms and activities of human herpesvirus 8 interleukin-6. J Virol 83:722-33
Chen, Daming; Choi, Young Bong; Sandford, Gordon et al. (2009) Determinants of secretion and intracellular localization of human herpesvirus 8 interleukin-6. J Virol 83:6874-82

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