Selection Pressure-Driven Evolution of the Epstein-Barr Virus-Encoded Oncogene LMP1 in Virus Isolates from Southeast Asia

Burrows, Jacqueline M.; Bromham, Lindell; Woolfit, Megan; Piganeau, Gwenaël; Tellam, Judy; Connolly, Geoff; Webb, Natasha; Poulsen, L M; Cooper, Leanne; Burrows, Scott R.; Moss, Denis J.; Haryana, Sofia Mubarika; Ng, Mun Hon; Nicholls, John M.; Khanna, Rajiv

doi:10.1128/jvi.78.13.7131-7137.2004

Cited by 40 publications

(35 citation statements)

References 32 publications

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“…The five LMP1 strains identified in the Thai population were also found in patients with lymphoma in Malaysia (Kim & Peh, 2003), with NPC in Thailand (Tiwawech et al, 2008), Indonesia (Burrows et al, 2004) and Vietnam (Nguyen- Van et al, 2008) and with T-cell diseases in Thailand (Saechan et al, 2006). The LMP1 strains found in this study have also been identified in other geographical areas (Edwards et al, 1999;Saechan et al, 2006;SitkiGreen et al, 2002SitkiGreen et al, , 2003, where the majority and distribution patterns of strains reflect geographical location.…”

Section: Discussionsupporting

confidence: 54%

“…Although this protein is essential for the oncogenic potential of EBV, little is known about sequence variation in the LMP1 gene of EBV isolates among the general population in South-east Asia. Only limited LMP1 sequences that have been isolated from patients with nasopharyngeal carcinoma (NPC) in Thailand, Indonesia and Vietnam and with lymphomas in Malaysia and Thailand have been reported (Burrows et al, 2004;Kim & Peh, 2003 (Burrows et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Epstein–Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups

Saechan

Settheetham-Ishida

Kimura

et al. 2010

Journal of General Virology

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Epstein-Barr virus (EBV) is ubiquitous in the human population and seroepidemiological studies have revealed that more than 90 % of adults are infected with the virus in Thailand. It has been suggested that latent membrane protein 1 (LMP1) variants may differ in their tumorigenicity and geographical localization. The distribution of LMP1 variants of EBV in the Thai population was studied. A total of 259 LMP1 sequences from ten Thai ethnic groups (Lahu, Lisu, Shan, Red Karen, White Karen, Hmong, Akha, Mlabri, Moken and Urak Lawoi) were studied using direct PCR sequencing. Nucleotide sequences corresponding to the C terminus of the LMP1, including previously published sequences from central and southern Thais, were used in the phylogenetic analysis. Five strains -the B95-8 prototype, China 1, China 2, Mediterranean (Med) and SEA 2 -were identified in ethnic groups in Thailand. The major strain and the distribution pattern differed by group and location. When the ethnic groups were classified by linguistic group, the prevalence of the SEA 2 strain was significantly different between Austro-Thais and other linguistic groups (P50.0001), whereas, among Tibeto-Burman linguistic groups, the prevalence of the Med strain was different between matrilocal and patrilocal groups (P50.0245). The distribution of LMP1 strains in ethnic minorities in Thailand is associated with ethnogeographical factors and the social/ marriage system. This study thus provides evidence for the importance of interactions between populations in virus diversity. INTRODUCTIONEpstein-Barr virus (EBV) is ubiquitous in human populations. Seroepidemiological studies have revealed that more than 90 % of adults are infected with the virus in Thailand (Mitarnun et al., 2002;Tiwawech et al., 2003). Once infected with EBV, humans continue to carry the virus in a small fraction of their B lymphocytes, probably for life (ThorleyLawson, 2001). The EBV genome is a linear, doublestranded DNA molecule of 172 kb and has reiterated 0.5 kb terminal repeats and a 3 kb internal direct repeat (Baer et al., 1984;. More than 85 genes are encoded in the EBV genome (Parker et al., 1990).At least five viral latent proteins are essential for B-cell immortalization; these are the EBV nuclear antigens EBNA1, EBNA2, EBNA3A and EBNA3C and latent membrane protein 1 (LMP1) (Izumi, 2001;Kaye et al., 1995).The nucleotide sequence of the LMP1 gene shows diversity and the distribution of LMP1 variants shows geographically specific localization (Lin et al., 1995). Although this protein is essential for the oncogenic potential of EBV, little is known about sequence variation in the LMP1 gene of EBV isolates among the general population in South-east Asia. RESULTSLMP1 nucleotide sequences corresponding to the Cterminal region were determined in 259 individuals belonging to ten ethnic groups (Table 1); the detection rate varied by ethnic group ranging from 10 to .50 %. The obtained sequences were translated into amino acids for the phylogenetic analyses. Five known strains -the B95-8 pro...

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Section: Discussionsupporting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Epstein–Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups

Saechan

Settheetham-Ishida

Kimura

et al. 2010

Journal of General Virology

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“…1). It is thought that LMP1 evades host immunity by having multiple variations as a result of positive selection [37]. These results suggest that EBV can evolve under the exposure to host immunity and survive in various substrains.…”

Section: Discussionmentioning

confidence: 89%

“…The sequence variations of vIL-10 were much smaller than those of LMP1, suggesting a weaker positive selection pressure for the IL-10 versus the LMP1 molecules [37,38]. vIL-10 functions as a cytokine, similar to hIL-10 [14,15,18,19].…”

Section: Discussionmentioning

confidence: 99%

The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates

et al. 2007

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A gene of the Epstein-Barr virus (EBV), BamHI-C fragment rightward reading frame 1 (BCRF1), codes viral interleukin-10 (vIL-10), which is a close homolog to human IL-10. EBV strain variations are known at EBV latent membrane protein 1 (LMP1), and the distinct forms of LMP1 have been identified. In order to further elucidate the variations of EBV strains, the BCRF1 (vIL-10) gene was analyzed using PCR-direct sequencing in African Burkitt's lymphoma (BL) cell lines Raji, P3HR-1, EB1 and Daudi, Japanese BL cell line Akata, lymphoblastoid cell line OB and 22 wild EBV isolates from eight gastric carcinoma tissues and 14 throat washes. We found only five variations of the vIL-10 gene in them with one silent mutation and three non-silent mutations. Raji had no mutation to the prototype gene of B95-8. EB1 and P3HR-1 had non-silent mutations in the sequences leading to the arginine/serine and threonine/proline interchanges at residues 4 and 166, respectively. The silent mutation was detected at valine 102 in Daudi and also in the Japanese cell lines Akata, OB and 20 (90.9%) of the wild EBV isolates. The type of variations in the vIL-10 gene had a common relationship with those in the LMP1 gene. All of the variants of valine 102 had China1-type LMP1 sequences except for Daudi with Med-type LMP1 and other minorities with B95-8 type LMP1. The conservativeness of vIL-10 with a few variations suggests the indispensability of the vIL-10 gene in EBV and that the variations of the vIL-10 gene may depend upon the geographical prevalence of the EBV strains. This is the first report regarding the variations of the vIL-10 gene in cell lines and other wild isolates.

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“…Many epitopes for CTL surveillance have been mapped in EBV antigens and correlated with MHC type. There is some clear evidence for epitope selection based on immune surveillance (Burrows et al 2004;Midgley et al 2003a, b;Nagamine et al 2007;Tang et al 2008;Lin et al 2004Lin et al , 2005Duraiswamy et al 2003). Evidence for positive selection also comes from ratios of non-synonymous to synonymous changes in the SNPs present in reading frames (Palser et al 2015).…”

Section: Broad Aspects Of Genome Variation-ebv Types Selection Forcementioning

confidence: 96%

Epstein–Barr Virus Strain Variation

Farrell

2015

Current Topics in Microbiology and Immunology

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What is wild-type Epstein-Barr virus and are there genetic differences in EBV strains that contribute to some of the EBV-associated diseases? Recent progress in DNA sequencing has resulted in many new Epstein-Barr virus (EBV) genome sequences becoming available. EBV isolates worldwide can be grouped into type 1 and type 2, a classification based on the EBNA2 gene sequence. Type 1 transforms human B cells into lymphoblastoid cell lines much more efficiently than type 2 EBV and molecular mechanisms that may account for this difference in cell transformation are now becoming understood. Study of geographic variation of EBV strains independent of the type 1/type 2 classification and systematic investigation of the relationship between viral strains, infection and disease are now becoming possible. So we should consider more directly whether viral sequence variation might play a role in the incidence of some EBV-associated diseases.

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Selection Pressure-Driven Evolution of the Epstein-Barr Virus-Encoded Oncogene LMP1 in Virus Isolates from Southeast Asia

Cited by 40 publications

References 32 publications

Epstein–Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups

Epstein–Barr virus strains defined by the latent membrane protein 1 sequence characterize Thai ethnic groups

The vIL-10 gene of the Epstein-Barr virus (EBV) is conserved in a stable manner except for a few point mutations in various EBV isolates

Epstein–Barr Virus Strain Variation

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