Fifty-two monoclonal PTLD were investigated for: 1). somatic hypermutation of IgV genes by direct sequencing of IgV rearrangements; 2). expression of BCL6, MUM1 and CD138 proteins by immunohistochemistry; 3). aberrant hypermethylation of DAP-kinase gene by methylation-specific polymerase chain reaction (PCR); 4). genotypic characterization of Epstein Barr virus (EBV) in EBV infected PTLD by PCR analysis of the prevalence of deletions in the carboxyterminal portion of the LMP1 gene and for the definition of type-1/type-2 EBV infection.
As oral cavity is the main location of Epstein-Barr virus (EBV) latency and shedding, and as EBV-encoded latent membrane protein-1 (LMP-1) has a crucial role in cell transformation, association between EBV infection, LMP-1 expression and oral malignancy is of interest.
Polymerase chain reaction was used to determine the LMP-1 gene sequence and demonstrate that the two tumours contained different clonal viral genomes, suggesting a central and specific role of EBV infection.
Although HLH is genetically distinct from XLP, our data suggest that both diseases share a common signal pathway, through either the mutation or LMP1-mediated suppression of the SAP gene, leading to overt T-cell activation and enhanced Th1 cytokine secretion in response to EBV infection.
We therefore investigated the incidence of latent EBV infection in a group of patients with leukemic low-grade B-NHL, as well as the incidence of viral latent membrane protein 1 (LMP1) oncoprotein expression in the same patient group.
We employed a newly developed genotyping technique with direct representational detection of LMP-1 gene sequences to study the molecular epidemiology of Epstein-Barr virus (EBV) infection in healthy individuals.
In this study, we investigated the diversity of the EBV genes (EBNA-1 and LMP-1) and the relationship between EBV variants and the clinical phenotypes in diseases associated with EBV infections in Chinese pediatric cases.
Tissues from 150 patients were also analyzed for the presence of latent EBV infection using in situ hybridization for EBV-encoded RNA (EBER) and immunohistochemistry for latent membrane protein (LMP1).
To further investigate the potential relationship of del-LMP-1 to EBV-LPDs associated with immunosuppression or immunodeficiency, we studied 39 EBV-associated lymphoproliferations (10 benign, 29 malignant) from four distinct clinical settings: posttransplant (4 malignant, 1 reactive); HIV+ (18 malignant, 2 reactive); nonimmunodeficiency malignant lymphoma (ML) (7 cases); and sporadic EBV infection with lymphoid hyperplasia (7 cases).
The induction of EGFR and A20 by LMP1 may be an important component of EBV infection in epithelial cells and could contribute to the development of epithelial malignancies such as NPC.
As the present study revealed four cases with positive LMP-1 immunostaining but negative EBER-1 ISH (1 HD, 3 NHL), LMP-1 alone should not be regarded as a tool to prove EBV infection.
Elucidation of the mechanisms involved in LMP1-induced genomic instability in nasopharyngeal epithelial cells will shed lights on the understanding of role of EBV infection in NPC development.
Our study suggests that these sequence variations of NPC-derived LMP1 may lead to a potential escape from host cell immune recognition, protecting latent EBV infection and causing an increase in tumorigenicity.
Epstein-Barr virus (EBV) infection is associated with many human neoplasms, in which EBV-derived latent membrane protein-1 (LMP1) appears to be critical, but its exact oncogenic mechanism remains to be defined.
Our findings help to elucidate the still enigmatic link between EBV infection and MS development, suggesting that myelin-reactive antibodies raised as a response toward EBV protein LMP1 are not truly cross-reactive but are primarily caused by epitope spreading.
Fibronectin is regarded as a prognosticator in NPC and its involvement in cell motility has been reported in EBV infection and viral latent membrane protein 1 (LMP1) overexpression NPC cell lines.
EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1).
Thus, antibodies induced against LMP1 during Epstein-Barr virus infection might act as inflammatory trigger by reacting with MBP, suggesting molecular mimicry in the mechanism of MS pathogenesis.
These data suggest new functions of the N terminus and transmembrane domains in LMP1 intra- and extracellular trafficking that are likely downstream of an interaction with CD63.<b>IMPORTANCE</b> EBV infection contributes to the development of cancers, such as nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin's disease, and posttransplant lymphomas, in immunocompromised or genetically susceptible individuals.
Together, these findings suggest that LMP1 modulates different post-translational modifications of SENP2 in order to modulate its biology and identify a third member of the sumoylation machinery that is manipulated by LMP1 during latent EBV infections, which can affect oncogenesis.