TY - JOUR
T1 - Inhibition of host kinase activity altered by the LMP2A signalosome - A therapeutic target for Epstein-Barr virus latency and associated disease
AU - Cooper, Lori
AU - Longnecker, Richard
N1 - Funding Information:
R. Longnecker is supported by Public Health Service grants CA62234, CA73507, and CA93444 from the National Cancer Institute and DE13127 from the National Institute of Dental and Craniofacial Research. R. Longnecker is a Stohlman Scholar of the Leukemia and Lymphoma Society of America. We would like to thank members of the Longnecker and Spear Laboratories for their help in these studies. In addition, we thank Toni Portis, Patrick Dennis, and Becca Katzman for kindly reading the manuscript prior to submission.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong latent infection in the majority of the human population. The virus resides in a latent state in B lymphocytes and is associated with a variety of cancers in the human host. In normal individuals, latent infection with EBV typically poses no health risk, but upon immunosuppression, either following organ transplantation or HIV infection, malignancies and lymphoproliferative diseases can result. Latent membrane protein 2A (LMP2A) is a virally encoded membrane protein that is expressed in EBV latent infection and in most of the tumors associated with EBV infection. Previous studies have indicated that LMP2A expression alters the activity of the Src family protein tyrosine kinases, the Syk protein tyrosine kinase, the Btk protein tyrosine kinase, and phosphatidylinositol 3-kinase (PI3-kinase). In this study, inhibitors of each of these kinases were tested using an in vitro system dependent on LMP2A expression for B cell colony formation in IL-7 containing methylcellulose media. Of the inhibitors tested, only piceatannol, a Syk tyrosine kinase inhibitor, demonstrated a specific effect on LMP2A expressing cells and not control cells. These studies provide a basis for targeting LMP2A function in EBV latency and may allow for the identification of novel therapeutics for the treatment or eradication of EBV latent infections and associated proliferative disorders.
AB - Epstein-Barr virus (EBV) is a human herpesvirus that establishes a lifelong latent infection in the majority of the human population. The virus resides in a latent state in B lymphocytes and is associated with a variety of cancers in the human host. In normal individuals, latent infection with EBV typically poses no health risk, but upon immunosuppression, either following organ transplantation or HIV infection, malignancies and lymphoproliferative diseases can result. Latent membrane protein 2A (LMP2A) is a virally encoded membrane protein that is expressed in EBV latent infection and in most of the tumors associated with EBV infection. Previous studies have indicated that LMP2A expression alters the activity of the Src family protein tyrosine kinases, the Syk protein tyrosine kinase, the Btk protein tyrosine kinase, and phosphatidylinositol 3-kinase (PI3-kinase). In this study, inhibitors of each of these kinases were tested using an in vitro system dependent on LMP2A expression for B cell colony formation in IL-7 containing methylcellulose media. Of the inhibitors tested, only piceatannol, a Syk tyrosine kinase inhibitor, demonstrated a specific effect on LMP2A expressing cells and not control cells. These studies provide a basis for targeting LMP2A function in EBV latency and may allow for the identification of novel therapeutics for the treatment or eradication of EBV latent infections and associated proliferative disorders.
KW - Epstein-Barr virus (EBV)
KW - Phosphatidylinositol 3-kinase
KW - Syk tyrosine kinase
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U2 - 10.1016/S0166-3542(02)00110-9
DO - 10.1016/S0166-3542(02)00110-9
M3 - Article
C2 - 12406506
AN - SCOPUS:0036888322
VL - 56
SP - 219
EP - 231
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 3
ER -