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Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo.
Cancer Res. 1999 Apr 01; 59(7):1485-91.CR

Abstract

The consistent presence of EBV genomes in certain tumor types (in particular, AIDS-related central nervous system lymphomas and nasopharyngeal carcinomas) may allow novel, EBV-based targeting strategies. Tumors contain the latent (transforming) form of EBV infection. However, expression of either of the EBV immediate-early proteins, BZLF1 and BRLF1, is sufficient to induce lytic EBV infection, resulting in death of the host cell. We have constructed replication-deficient adenovirus vectors expressing the BZLF1 or BRLF1 immediate-early genes and examined their utility for killing latently infected lymphoma cells in vitro and in vivo. We show that both the BZLF1 and BRLF1 vectors efficiently induce lytic EBV infection in Jijoye cells (an EBV-positive Burkitt lymphoma cell line). Furthermore, lytic EBV infection converts the antiviral drug, ganciclovir (GCV), into a toxic (phosphorylated) form, which inhibits cellular as well as viral DNA polymerase. When Jijoye cells are infected with the BZLF1 or BRLF1 adenovirus vectors in the presence of GCV, viral reactivation is induced, but virus replication is inhibited (thus preventing the release of infectious EBV particles); yet cells are still efficiently killed. Finally, we demonstrate that the BZLF1 and BRLF1 adenovirus vectors induce lytic EBV infection when they are directly inoculated into Jijoye cell tumors grown in severe combined immunodeficiency mice. These results suggest that induction of lytic EBV infection in tumors, in combination with GCV, may be an effective strategy for treating EBV-associated malignancies.

Authors+Show Affiliations

UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10197618

Citation

Westphal, E M., et al. "Induction of Lytic Epstein-Barr Virus (EBV) Infection in EBV-associated Malignancies Using Adenovirus Vectors in Vitro and in Vivo." Cancer Research, vol. 59, no. 7, 1999, pp. 1485-91.
Westphal EM, Mauser A, Swenson J, et al. Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. Cancer Res. 1999;59(7):1485-91.
Westphal, E. M., Mauser, A., Swenson, J., Davis, M. G., Talarico, C. L., & Kenney, S. C. (1999). Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. Cancer Research, 59(7), 1485-91.
Westphal EM, et al. Induction of Lytic Epstein-Barr Virus (EBV) Infection in EBV-associated Malignancies Using Adenovirus Vectors in Vitro and in Vivo. Cancer Res. 1999 Apr 1;59(7):1485-91. PubMed PMID: 10197618.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of lytic Epstein-Barr virus (EBV) infection in EBV-associated malignancies using adenovirus vectors in vitro and in vivo. AU - Westphal,E M, AU - Mauser,A, AU - Swenson,J, AU - Davis,M G, AU - Talarico,C L, AU - Kenney,S C, PY - 1999/4/10/pubmed PY - 1999/4/10/medline PY - 1999/4/10/entrez SP - 1485 EP - 91 JF - Cancer research JO - Cancer Res VL - 59 IS - 7 N2 - The consistent presence of EBV genomes in certain tumor types (in particular, AIDS-related central nervous system lymphomas and nasopharyngeal carcinomas) may allow novel, EBV-based targeting strategies. Tumors contain the latent (transforming) form of EBV infection. However, expression of either of the EBV immediate-early proteins, BZLF1 and BRLF1, is sufficient to induce lytic EBV infection, resulting in death of the host cell. We have constructed replication-deficient adenovirus vectors expressing the BZLF1 or BRLF1 immediate-early genes and examined their utility for killing latently infected lymphoma cells in vitro and in vivo. We show that both the BZLF1 and BRLF1 vectors efficiently induce lytic EBV infection in Jijoye cells (an EBV-positive Burkitt lymphoma cell line). Furthermore, lytic EBV infection converts the antiviral drug, ganciclovir (GCV), into a toxic (phosphorylated) form, which inhibits cellular as well as viral DNA polymerase. When Jijoye cells are infected with the BZLF1 or BRLF1 adenovirus vectors in the presence of GCV, viral reactivation is induced, but virus replication is inhibited (thus preventing the release of infectious EBV particles); yet cells are still efficiently killed. Finally, we demonstrate that the BZLF1 and BRLF1 adenovirus vectors induce lytic EBV infection when they are directly inoculated into Jijoye cell tumors grown in severe combined immunodeficiency mice. These results suggest that induction of lytic EBV infection in tumors, in combination with GCV, may be an effective strategy for treating EBV-associated malignancies. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/10197618/Induction_of_lytic_Epstein_Barr_virus__EBV__infection_in_EBV_associated_malignancies_using_adenovirus_vectors_in_vitro_and_in_vivo_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10197618 DB - PRIME DP - Unbound Medicine ER -