Detection and prevalence of the "f" variant of Epstein-Barr virus in southern China.
ABSTRACT The "f" variant of Epstein-Barr virus (EBV) may have an association with the development and/or maintenance of nasopharyngeal carcinoma (NPC) among Southern Chinese. This variant is detected at a higher frequency among individuals with elevated IgA antibody levels against EBV capsid antigen who have no detectable NPC and in NPC patients as compared to healthy individuals or patients who are in remission for NPC for over 3 years. Conversion or replacement of the f variant by the prototype BamHI F virus usually occurs by 3 to 4 years after radiotherapy. By 5 years post-therapy the majority of people in remission for NPC no longer harbor the f variant in their oropharynx. Eradication of this f variant, however, does not appear essential for maintenance of a disease-free state since several patients harboring this variant were in remission for NPC for up to 21 years. The virus strain detected directly in the nasopharynx is not always identical to that seen in the oropharynx. Dual infection was commonly observed in throat washings of NPC patients although the biopsy from tumors harbored unique strains of EBV.
Article: Epstein-barr virus nuclear antigen 1 sequences in endemic and sporadic Burkitt's lymphoma reflect virus strains prevalent in different geographic areas.[show abstract] [hide abstract]
ABSTRACT: The Epstein-Barr virus (EBV) nuclear antigen EBNA1 is the only viral protein detectably expressed in virus genome-positive Burkitt's lymphoma (BL); recent work has suggested that viral strains with particular EBNA1 sequence changes are preferentially associated with this tumor and that, within a patient, the tumor-associated variant may have arisen de novo as a rare mutant of the dominant preexisting EBV strain (K. Bhatia, A. Raj, M. J. Gutierrez, J. G. Judde, G. Spangler, H. Venkatesh, and I. T. Magrath, Oncogene 13:177-181, 1996). In the present work we first study 12 BL patients and show that the virus strain in the tumor is identical in EBNA1 sequence and that it is matched at several other polymorphic loci to the dominant strain rescued in vitro from the patient's normal circulating B cells. We then analyze BL-associated virus strains from three different geographic areas (East Africa, Europe, and New Guinea) alongside virus isolates from geographically matched control donors by using sequence changes in two separate regions of the EBNA1 gene (N-terminal codons 1 to 60 and C-terminal codons 460 to 510) to identify the EBNA1 subtype of each virus. Different geographic areas displayed different spectra of EBNA1 subtypes, with only limited overlap between them; even type 2 virus strains, which tended to be more homogeneous than their type 1 counterparts, showed geographic differences at the EBNA1 locus. Most importantly, within any one area the EBNA1 subtypes associated with BL were also found to be prevalent in the general population. We therefore find no evidence that Burkitt lymphomagenesis involves a selection for EBV strains with particular EBNA1 sequence changes.Journal of Virology 03/1999; 73(2):965-75. · 5.40 Impact Factor
Article: Epstein-Barr virus associated gastric carcinoma: a report from Iran in the last four decades.[show abstract] [hide abstract]
ABSTRACT: Epstein-Barr virus has been proved to be associated with many of the human malignancy including gastric carcinoma, one of the most important human malignancies in the world. There has been no study about the presence of EBV in gastric adenocarcinoma in Iran. We examined the presence of EBV in 273 formalin fixed paraffin-embedded cases of gastric carcinoma from Cancer institute of Tehran University, from 1969 to 2004. In situ hybridization of EBV-encoded small RNA-1 (EBER-1) was conducted. The strain of positive cases was examined by means of polymerase chain reaction and/or restriction fragment length polymorphism analysis. We found 9 (3%; 95% CI = 1-5%) EBV positive cases. The gender difference was not statisticaly significant. The proportion of EBV-GC cases in diffuse type was higher than intestinal type (OR = 0.08; 95% CI = 0.002-0.64). EBV-GC cases had no relation with age, location and invasion. Six out of 9 EBV-GC cases were born during the period between 1928 and 1930. All 9 cases were Type A. Prototype F was seen in 6 out of 8 cases. Type "i" was found in 8 cases and type I in 1 case. XhoI+ and XhoI- polymorphism accounted 6 and 3 of the cases, respectively. Our study is the first to describe the frequency of EBV-GC in Iran and the Middle East, highlighting a very low prevalence with specific clinicopathologic features. The predominance of EBV-GC birth year in a fixed period, suggests that EBV infection or other events at early childhood may be related to the development of EBV-GC later in the life. The predominance of the type "i" and XhoI+ cases are contradictory to other studies in Asia and is similar to what is reported from Latin American countries.Diagnostic Pathology 02/2007; 2:25. · 1.64 Impact Factor
Article: Sequence variations of latent membrane protein 2A in Epstein-Barr virus-associated gastric carcinomas from Guangzhou, southern China.[show abstract] [hide abstract]
ABSTRACT: Latent membrane protein 2A (LMP2A), expressed in most Epstein-Barr virus (EBV)-associated malignancies, has been demonstrated to be responsible for the maintenance of latent infection and epithelial cell transformation. Besides, it could also act as the target for a CTL-based therapy for EBV-associated malignancies. In the present study, sequence variations of LMP2A in EBV-associated gastric carcinoma (EBVaGC) and healthy EBV carriers from Guangzhou, southern China, where nasopharyngeal carcinoma (NPC) is endemic, were investigated. Widespread sequence variations in the LMP2A gene were found, with no sequence identical to the B95.8 prototype. No consistent mutation was detected in all isolates. The immunoreceptor tyrosine-based activation motif (ITAM) and PY motifs in the amino terminus of LMP2A were strictly conserved, suggesting their important roles in virus infection; while 8 of the 17 identified CTL epitopes in the transmembrane region of LMP2A were affected by at least one point mutation, which may implicate that the effect of LMP2A polymorphisms should be considered when LMP2A-targeted immunotherapy is conducted. The polymorphisms of LMP2A in EBVaGC in gastric remnant carcinoma (GRC) were for the first time investigated in the world. The LMP2A sequence variations in EBVaGC in GRC were somewhat different from those in EBVaGC in conventional gastric carcinoma. The sequence variations of LMP2A in EBVaGC were similar to those in throat washing of healthy EBV carriers, indicating that these variations are due to geographic-associated polymorphisms rather than EBVaGC-associated mutations. This, to our best knowledge, is the first detailed investigation of LMP2A polymorphisms in EBVaGC in Guangzhou, southern China, where NPC is endemic.PLoS ONE 01/2012; 7(3):e34276. · 4.09 Impact Factor