title: Carboxy-terminal sequence variation of LMP1 gene in Epstein-Barr-virus-associated mononucleosis and tumors from Serbian patients.
abstract: Seven strains of Epstein-Barr virus (EBV) are defined based on C-terminal sequence variations of the latent membrane protein 1 (LMP1). Some strains, especially those with a 30-bp deletion, are thought to be related to tumorigenic activity and geographical localization. The aims of the study were to determine the prevalence of different LMP1 strains and to investigate sequence variation in the C-terminal region of LMP1 in Serbian isolates. This study included 53 EBV-DNA-positive plasma and tissue block samples from patients with mononucleosis syndrome, renal transplantation, and tumors, mostly nasopharyngeal carcinoma. The sequence of the 506-bp fragment of LMP1 C terminus was used for phylogenetic analyses and identification of LMP1 strains, deletions, and mutations. The majority of isolates were non-deleted (66%), and the rest had 30-bp, rare 69-bp, or yet unknown 27-bp deletions, which were not related to malignant or non-malignant isolate origin. However, the majority of 69-bp deletion isolates were derived from patients with nasopharyngeal carcinoma. Less than five 33-bp repeats were found in the majority of non-deleted isolates (68.6%), whereas most 69-bp deletion isolates (75%) had five or six repeats. Serbian isolates were assigned to four LMP1 strains: B95-8 (32.1%), China 1 (24.5%), North Carolina (NC; 18.9%), and Mediterranean (Med; 24.5%). In NC isolates, three new mutations unique for this strain were identified. EBV EBNA2 genotypes 1 and 2 were both found, with dominance of genotype 1 (90.7%). This study demonstrated noticeable geographical-associated characteristics in the LMP1 C terminus of investigated isolates.
authors.affiliation: Institute of Microbiology and Immunology, University of Belgrade, Serbia. anadjukic@med.bg.ac.rs
authors.forename: Ana
authors.initials: A
authors.lastname: Banko
authors.forename: Ivana
authors.initials: I
authors.lastname: Lazarevic
authors.forename: Maja
authors.initials: M
authors.lastname: Cupic
authors.forename: Goran
authors.initials: G
authors.lastname: Stevanovic
authors.forename: Ivan
authors.initials: I
authors.lastname: Boricic
authors.forename: Tanja
authors.initials: T
authors.lastname: Jovanovic
mesh_terms: D002277:Carcinoma; D016000:Cluster Analysis; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification*; D006801:Humans; D007244:Infectious Mononucleosis / Q000821:virology*; D008969:Molecular Sequence Data; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000821:virology*; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D055771:Serbia; D014763:Viral Matrix Proteins / Q000235:genetics*
chemical_list: D004279:DNA, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins