title: Analysis of the Variability of Epstein-Barr Virus Genes in Infectious Mononucleosis: Investigation of the Potential Correlation with Biochemical Parameters of Hepatic Involvement.
abstract: BACKGROUND
  Primary Epstein-Barr virus (EBV) infection is usually asymptomatic, although at times it results in the benign lymphoproliferative disease, infectious mononucleosis (IM), during which almost half of patients develop hepatitis. The aims of the present study are to evaluate polymorphisms of EBV genes circulating in IM isolates from this geographic region and to investigate the correlation of viral sequence patterns with the available IM biochemical parameters.
  
  
  METHODS
  The study included plasma samples from 128 IM patients. The genesEBNA2, LMP1, andEBNA1were amplified using nested-PCR.EBNA2genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation ofLMP1andEBNA1included sequence, phylogenetic, and statistical analyses.
  
  
  RESULTS
  The presence of EBV DNA in plasma samples showed correlation with patients' necessity for hospitalization (p=0.034). The majority of EBV isolates was genotype 1. LMP1 variability showed 4 known variants, and two new deletions (27-bp and 147-bp). Of the 3 analyzed attributes ofLMP1isolates, the number of 33-bp repeats less than the reference 4.5 was the only one that absolutely correlated with the elevated levels of transaminases. EBNA1 variability was presented by prototype subtypes. A particular combination ofEBNA2, LMP1, andEBNA1polymorphisms,deleted LMP1/P-thrandnon-deleted LMP1/P-ala, as well asgenotype 1/ 4.5 33-bp LMP1 repeatsorgenotype 2/ 4.5 33-bp LMP1 repeatsshowed correlation with elevated AST (aspartate aminotransferase) and ALT (alanine transaminase).
  
  
  CONCLUSIONS
  This is the first study which identified the association between EBV variability and biochemical parameters in IM patients. These results showed a possibility for the identification of hepatic related diagnostic EBV markers.
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Banko
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Lazarevic
authors.affiliation: Clinics of Infectious and Tropical Diseases, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Goran
authors.initials: G
authors.lastname: Stevanovic
authors.affiliation: Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Andja
authors.initials: A
authors.lastname: Cirkovic
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Karalic
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Maja
authors.initials: M
authors.lastname: Cupic
authors.affiliation: Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Banko
authors.affiliation: Clinic of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Jovica
authors.initials: J
authors.lastname: Milovanovic
authors.affiliation: Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Serbia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
keywords: EBV; LMP1; gene polymorphism; infectious mononucleosis; transaminase