Epstein‐barr virus (EBV) in healthy carriers: Distribution of genotypes and 30 bp deletion in latent membrane protein‐1 (LMP‐1) oncogene

Abstract

There are two types of Epstein Barr virus (EBV): EBV-1 and EBV-2, distinguished by genomic polymorphism in the genes encoding the nuclear antigens (EBNA-2, -3A, -3B, -3C). Latent membrane protein 1 (LMP-1) is an EBV protein with known oncogenic properties. Different variants had been described; among them, a 30 base pair (bp) deletion (del-LMP-1) had been reported in benign and malignant pathologies, but there is little information about its frequency in healthy populations. The aim of this study was to determine the distribution of the EBV genotypes and the 30 bp deletion frequency, in EBV healthy carriers from Argentina. Analysis of EBNA-3C and LMP-1 genes were done by polymerase chain reaction (PCR) followed by Southern blot hybridization on DNA of peripheral blood mononuclear cells (PBMCs) from blood bank donors. EBV-1 was present in 75.9% of samples, EBV-2 in 14.6%, and co-infections with both types in 6.5%. The deleted LMP-1 variant was found in 7.4% of analyzed samples, corresponding 3.2% to deleted variant alone and 4.2% to co-infections with non-deleted form. The non-deleted variant was found in 64.6% whereas in the remaining 28%, no PCR product was detected. These results showed that EBV-1 was the more prevalent type in healthy carriers of Argentina, similar to reports from others countries. A predominance of the non-deleted LMP-1 variant was observed. The presence of co-infections with both types and variants demonstrated that healthy individuals may also harbor multiple EBV infections.

Distinctive Epstein-Barr Virus Variants Associated with Benign and Malignant Pediatric Pathologies: LMP1 Sequence Characterization and Linkage with Other Viral Gene Polymorphisms

“…These results confirmed previous observations in which an association between del30 and high rep33 numbers and between del30 and ins15 had been documented in HL samples from Argentina and Brazil (14). In contrast, in our region a very low incidence of del30 variants and a low number of rep33 copies was previously described among healthy individuals (4,8). To the best of our knowledge, the 15-bp insertion encoding a JAK3 signaling motif has been described only within the third repeat of rep33 in B95.8-related sequences (14,28,40).…”

“…adults with IM were infected with multiple LMP1 variants, and their distribution fluctuated dynamically between OS and PBMC over time (8,27,35,36); however, no coinfections with LMP1 variants were observed in the pediatric patients with IM studied here. On the other hand, coinfection with two EBV variants was detected in a low proportion (3/15) of IM patients in different compartments at some time point during the study when other EBV genes were assessed (Table 3) (24,25).…”

“…Particularly in Argentina, the deleted LMP1 variant was previously preferentially detected in tumor samples rather than in samples from healthy individuals, either adults (8,9) or children (5). The predominance of the del30 variant within tumors also was described in the rest of South America and Mexico, and it is in this geographic region that this distinct distribution scheme is more clearly observed (6,7,11,14,18).…”

Epstein–Barr virus BZLF1 gene promoter variants in pediatric patients with acute infectious mononucleosis: Its comparison with pediatric lymphomas

“…Most of the pediatric IM cases described here, 9/10, were infected with EBV1 and only 1 patient presented with EBV2 infection. This is in accordance with Correa et al [2004], who described that 75.9% of adult healthy carriers from Argentina were infected with EBV1. Interestingly, no pediatric patient evidenced co-infection with both EBV1 and EBV2, in contrast to the 6.5% co-infection described in adult healthy carriers by Correa et al [2004].…”

Detection of polyomaviruses and herpesviruses in human adrenal tumors

“…Moreover, the 30 bp deletion of the LMP-1 gene, which has been associated with a higher oncogenic potential (Knecht et al, 1993), was revealed only in EBV DNA from a normal adrenal gland. This distribution of EBV genotypes and 30 bp Polyomaviruses and herpesviruses in human adrenal tumors L Barzon et al deleted LMP-1 variant is similar to the prevalence observed in blood samples from EBV healthy carriers attending our Clinical Microbiology Laboratory in Padova (unpublished observations) and to the prevalence reported in other institutions (Gratama and Ernberg, 1995;Correa et al, 2004). To assess whether EBV infection in adrenal tissues was latent or lytic, we analysed expression of transcripts of EBV latent genes (EBER, EBNA-1, EBNA-2, EBNA-3C, LMP-1 and LMP-2) by reverse transcription (RT)-PCR, as reported (Isobe et al, 2004), and expression of EBNA-1 protein and EBV early antigen-diffuse (EA-D), which is expressed during lytic activation, by immunohistochemistry.…”