Journal of Medical Virology 81:1912–1917 (2009) Epstein–Barr Virus BZLF1 Gene Promoter Variants in Pediatric Patients With Acute Infectious Mononucleosis: Its Comparison With Pediatric Lymphomas Mario Alejandro Lorenzetti, 1 * Marina Ine ´ s Gutie ´ rrez, 2 Jaime Altcheh, 3 Guillermo Moscatelli, 3 Samanta Moroni, 3 Paola Andrea Chabay, 1 and Marı ´a Victoria Preciado 1 1 Pathology Division, Molecular Biology Laboratory,Ricardo Gutie´rrez Childrens Hospital, Buenos Aires, Argentina 2 Molecular Biology Division, Dr. Stamboulian Clinical Analysis Laboratory, Buenos Aires, Argentina 3 Parasitology and Chagas Disease Laboratory, Ricardo Gutie´rrez Childrens Hospital, Buenos Aires, Argentina Epstein–Barr virus genotypes can be distin- guished by polymorphic variations in the genes encoding EBNA2, 3A, 3B, and 3C. The immediate early gene BZLF1 plays a key role in modulating the switch from latency to lytic replication and therefore enabling viral propagation. The aim of this study was to investigate and compare BZLF1 promoter sequence (Zp) variation in pediatric infectious mononucleosis (IM) and in pediatric EBV positive lymphoma biopsies. Zp was sequenced from peripheral blood mononuclear cells (PBMC) and throat swabs from 10 patients with IM at the time of diagnosis (D0) and during convalescence; and from 13 lymphoma biopsies. Zp  P and Zp  V3 variants were found in eight and one IM patients, as well as in five and six tumor biopsies, respectively. A correlation between viral genotype and Zp variant was found significant for Zp  V3 and EBV2 (P ¼ 0.0002). One IM patient harbored two concomitant Zp variants. Regardless of anatomical compartment or stage of disease all IM patients displayed the same Zp variant along the course of the study. No new infections or adaptative selection of different variants was evidenced. A new Zp variant (Zp  V3 þ 49) was described in two Hodgkin lymphomas, but not in IM. This is the first study to describe Zp variants compartmentalization in children with acute EBV infection and convales- cence in a developing country; and comparing them with Zp variants in pediatric lymphomas from the same geographic area. J. Med. Virol. 81:1912–1917, 2009. ß 2009 Wiley-Liss, Inc. KEY WORDS: BZLF1 variants; Epstein–Barr virus; pediatric infectious mononucleosis; pediatric lym- phoma INTRODUCTION Epstein–Barr virus (EBV), a member of the gamma subfamily of the large Herpesviridae family, is an oncogenic, lymphotropic virus widely spread through- out the world. Over 90% of the human population shows evidence of past infection. Like other herpesvirus, it displays two forms of infection: lytic, related to primary infection, and latent, related to the maintenance of the virus in the infected individual and sometimes associ- ated with human cancers. Moreover, the switch from latency to lytic infection is required for virus replication and propagation among individuals [Cohen, 2000]. The virus establishes persistent infection in B cells, and continuously reactivates to produce infectious viral particles for transmission [Kieff and Rickinson, 2006]. The harmonious host–virus co-existence is the result of a long history with mutual adaptation, based on variation in the viral gene expression in different types of infected cells and the finely tuned immune response of the host [Klein et al., 2007]. In developing regions, like Argentina, primary EBV infection occurs within a few months to a few years after birth, and EBV seroconversion is almost universal by the age of 6 years [Chabay et al., 1999; Chan et al., 2001 and references herein]. Conversely, in industrialized countries, EBV infection occurs mostly during the second and third decade of life. Pediatric EBV infection is usually asymptomatic, but occasionally may cause infectious Grant sponsor: National Agency for Science and Technology Promotion PICT 2005 (partial support); Grant number: n838217. *Correspondence to: Mario Alejandro Lorenzetti, Pathology Division, Molecular Biology Laboratory, Ricardo Gutie ´rrez Chil- dren Hospital, Gallo 1330, C1425EFD Buenos Aires, Argentina. E-mail: marioloren@yahoo.com.ar Accepted 1 July 2009 DOI 10.1002/jmv.21616 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2009 WILEY-LISS, INC.