TY - JOUR
T1 - Eradication of latent Epstein-Barr virus by hydroxyurea alters the growth-transformed cell phenotype
AU - Chodosh, James
AU - Holder, Virgil P.
AU - Gan, Yan Jun
AU - Belgaumi, Asim
AU - Sample, Jeffery
AU - Sixbey, John W.
N1 - Funding Information:
Received 28 August 1997; revised 19 November 1997. Presented in part: National AIDS Malignancy Conference, Bethesda, Maryland, April 1997 (abstract 146). Animal experimentation guidelines of St. Jude Children’s Research Hospital were followed in the conduct of animal studies described. Financial support: NIH (CA-67372, CA-73544, CA-21765, DE-12187; AI-07372 to J.C.); American Lebanese Syrian Associated Charities. Reprints or correspondence: Dr. John W. Sixbey, Depts. of Infectious Diseases and Virology & Molecular Biology, St. Jude Children’s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105 ([email protected]). Present affiliation: Dean McGee Eye Institute, University of Oklahoma, Oklahoma City (J.C.); Children’s Cancer Center, King Faisal Specialist Hospital, Riyadh, Saudi Arabia (A.B.).
PY - 1998
Y1 - 1998
N2 - The hallmark of infection by human herpesviruses, life-long persistence in the host, is unaffected by current antiviral therapies effective against replication of virus. In vitro studies indicated that low concentrations of the ribonucleotide reductase inhibitor, hydroxyurea, completely eliminated Epstein-Barr virus (EBV) episomes from latently infected Burkitt's lymphoma (BL) cell subsets, providing the first example of chemotherapeutic eradication of a latent herpesvirus from any cell population. Unlike parental EBV-positive BL cells, virus-free cell progeny from one treated cell line no longer exhibited the malignant phenotype in tumorigenicity assays. Hydroxyurea-treated primary B lymphocytes immortalized by EBV ceased to proliferate as episomes were lost. The altered growth phenotype of both BL cells and immortalized primary B cells suggests that latent EBV is an appropriate and accessible therapeutic target for treatment of some EBV- induced lymphoproliferations.
AB - The hallmark of infection by human herpesviruses, life-long persistence in the host, is unaffected by current antiviral therapies effective against replication of virus. In vitro studies indicated that low concentrations of the ribonucleotide reductase inhibitor, hydroxyurea, completely eliminated Epstein-Barr virus (EBV) episomes from latently infected Burkitt's lymphoma (BL) cell subsets, providing the first example of chemotherapeutic eradication of a latent herpesvirus from any cell population. Unlike parental EBV-positive BL cells, virus-free cell progeny from one treated cell line no longer exhibited the malignant phenotype in tumorigenicity assays. Hydroxyurea-treated primary B lymphocytes immortalized by EBV ceased to proliferate as episomes were lost. The altered growth phenotype of both BL cells and immortalized primary B cells suggests that latent EBV is an appropriate and accessible therapeutic target for treatment of some EBV- induced lymphoproliferations.
UR - http://www.scopus.com/inward/record.url?scp=0031900086&partnerID=8YFLogxK
U2 - 10.1086/515290
DO - 10.1086/515290
M3 - Article
C2 - 9593003
AN - SCOPUS:0031900086
SN - 0022-1899
VL - 177
SP - 1194
EP - 1201
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 5
ER -
