Povezanost genetičke varijabilnosti Epštajn-Bar virusa i oboljenja udruženih sa Epštajn-Bar virusnom infekcijom
Correlation between Epstein-Barr virus genetic variability and Epstein-Barr virus-associated diseases
Author
Banko, Ana V.Mentor
Jovanović, TanjaCommittee members
Ćupić, Maja
Lazarević, Ivana

Stevanović, Goran

Milašin, Jelena

Metadata
Show full item recordAbstract
UVOD: Primarna Epstein-Barr virusna (EBV) infekcija može se manifestovati kao
infektivna mononukloza (IM). Takođe, EBV infekcija može predstavljati važnu kariku u
etiologiji velikog broja tumora, među kojima su najbrojniji limfomi, nazofaringealni (NFK)
i gastrični karcinom, kao i limfoproloferativne bolesti kod imunosuprimiranih pacijenata.
Brojna su istraživanja koja nagoveštavaju vezu između karakteristika pojedinih EBV
genotipova i onkogenog potencijala. Pretpostavlja se i da postoji veza između geografske
specifičnosti virusa sa potencijalno onkogenom strukturom njegovog genoma.
CILJEVI: Ovim istraživanjem utvrđuje se dominacija EBV genotipa i određuju LMP-1
varijante i EBNA-1 subtipovi. Takođe, ciljevi se odnose i na identifikaciju novih i
geografski specifičnih mutacija, kao i utvrđivanje moguće povezanosti polimorfizama
različitih EBV gena, identifikovanih mutacija i prirode oboljenja.
MATERIJAL I METODOLOGIJA: Studija je obuhvatila 360 pacijenata sa IM,
transplanti...ranim organom (T) ili NFK tipa UCNT (engl. undifferentiated carcinoma of
nasopharyngeal type). Korišćeni su uzorci krvi IM i T pacijenata, kao i parafinski kalupi
tkiva UCNT pacijenata. Nested-PCR metod korišćen je za dokazivanje EBNA-2, LMP-1 i
EBNA-1 gena, kao i za genotipizaciju EBNA-2 gena. Nakon DNK sekvenciranja specifičnih
regiona LMP-1 i EBNA-1 gena, sledila je filogenetska analiza dobijenih sekvenci. Obrađene
sekvence koristile su se za uzajamno poređenje varijabilnosti EBV gena, kao i za poređenje
sa kliničkim parametrima pojedinačnih oboljenja.
REZULTATI: Devedeset uzoraka (25%) bilo je pozitivno na prisustvo EBV DNK Dominantan genotip EBNA-2 izolata bio je genotip 1 (89,61%). Identifikovano je 4 od
sedam poznatih LMP-1 varijanti: B95-8, Kina 1, SK (Severna Karolina) i Med (Mediteran) i
2, do sada nepoznate, varijante Srb 1 i Srb 2 (Srbija 1 i 2). Najučestalija bila je varijanta
B95-8 (31%), a dokazana je i statistički značajna razlika u distribuciji varijanti među oboljenjima (p=0,039). LMP-1 delecije su otkrivene kod 39% izolata, i to: dve poznate
delecije od 30-bp i 69-bp, i dve novoidentifikovane delecije od 27-bp i 147-bp...
INTRODUCTION: Primary Epstein-Barr virus (EBV) infection could result in infectious
mononucleosis (IM). Also, EBV infection has an important role in etiology of numerous
tumors: lymphomas, nasopharyngeal (NPC) carcinoma, gastric carcinoma, and
lymphoproliferative diseases in immunocompromised patients. There are many studies
which suggest the association between EBV genotypes and oncogenic potential of this
virus. It is also assumed that geographical specificity of EBV genome could correlate with
potentially oncogenic structure of viral genome.
AIMS: The aims of this study were to determine the prevalence of EBV genotypes and to
identify LMP-1 variants and EBNA-1 subtypes. The aims also included identification of
new and geographical specific mutations, as well as investigation of possible association
between EBV genes polymorphisms, detected mutations and disease characteristics.
MATERIALS AND METHODS: This research included 360 patients with IM, transplanted
organ (T) or ...NPC (type UCNT, undifferentiated carcinoma of nasopharyngeal type). Blood
samples from IM and T patients, as well as paraffin embedded tissue blocks from UCNT
patients were included. Nested-PCR was used for detection of EBNA-2, LMP-1 and EBNA-1
genes, and also for EBNA-2 genotyping. After DNA sequencing of selected regions of LMP-
1 and EBNA-1 genes, phylogenetic analysis of obtained sequences were performed.
Finally, the sequences were used for investigation of correlation between EBV genes
variabilities or between gene variabilities and clinical characteristics od disease.
RESULTS: EBV DNA was present in 90 samples (25%). Among two EBNA-2 genotypes, genotype 1 was dominant (89,61%). Four out of 7 known LMP-1 variants were identified:
B95-8, China 1, NC (North Carolina), Med (Mediterranean). Moreover, 2 new variants
were detected: Srb 1 and Srb 2 (Serbia 1 and 2). The most frequent was B95-8 (31%).
There was statistically significant difference in variant distribution between diseases
(p=0,039). LMP-1 deletions were detected in 39% isolates: two known 30-bp i 69-bp, and
two yet unknown 27-bp i 147-bp...