Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus

Marina I. Gutiérrez, Muna M. Ibrahim, Janet K. Dale, Timothy Charles Greiner, Stephen E. Straus, Kishor Bhatia

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominately associated with nonmalignant diseases such as acute infectious mononucleosii (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases. Methods: Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided. Results: Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84% of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<.001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<.001). Zp-V4 was independent of the EBV type. Conclusions: Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies.

Original languageEnglish (US)
Pages (from-to)1757-1763
Number of pages7
JournalJournal of the National Cancer Institute
Volume94
Issue number23
StatePublished - Dec 4 2002

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Satellite Viruses
Human Herpesvirus 4
Carcinogens
Cercopithecine Herpesvirus 1
Neoplasms
Epstein-Barr Virus Infections
Regulator Genes
DNA Sequence Analysis
Non-Hodgkin's Lymphoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Gutiérrez, M. I., Ibrahim, M. M., Dale, J. K., Greiner, T. C., Straus, S. E., & Bhatia, K. (2002). Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus. Journal of the National Cancer Institute, 94(23), 1757-1763.

Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus. / Gutiérrez, Marina I.; Ibrahim, Muna M.; Dale, Janet K.; Greiner, Timothy Charles; Straus, Stephen E.; Bhatia, Kishor.

In: Journal of the National Cancer Institute, Vol. 94, No. 23, 04.12.2002, p. 1757-1763.

Research output: Contribution to journalArticle

Gutiérrez, MI, Ibrahim, MM, Dale, JK, Greiner, TC, Straus, SE & Bhatia, K 2002, 'Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus', Journal of the National Cancer Institute, vol. 94, no. 23, pp. 1757-1763.
Gutiérrez, Marina I. ; Ibrahim, Muna M. ; Dale, Janet K. ; Greiner, Timothy Charles ; Straus, Stephen E. ; Bhatia, Kishor. / Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus. In: Journal of the National Cancer Institute. 2002 ; Vol. 94, No. 23. pp. 1757-1763.
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abstract = "Background: Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominately associated with nonmalignant diseases such as acute infectious mononucleosii (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases. Methods: Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided. Results: Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84{\%} of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<.001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<.001). Zp-V4 was independent of the EBV type. Conclusions: Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies.",
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T1 - Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus

AU - Gutiérrez, Marina I.

AU - Ibrahim, Muna M.

AU - Dale, Janet K.

AU - Greiner, Timothy Charles

AU - Straus, Stephen E.

AU - Bhatia, Kishor

PY - 2002/12/4

Y1 - 2002/12/4

N2 - Background: Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominately associated with nonmalignant diseases such as acute infectious mononucleosii (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases. Methods: Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided. Results: Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84% of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<.001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<.001). Zp-V4 was independent of the EBV type. Conclusions: Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies.

AB - Background: Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominately associated with nonmalignant diseases such as acute infectious mononucleosii (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases. Methods: Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided. Results: Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84% of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<.001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<.001). Zp-V4 was independent of the EBV type. Conclusions: Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies.

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