Sequence variation of Epstein-Barr virus (EBV) BZLF1 gene in EBV-associated gastric carcinomas and nasopharyngeal carcinomas in Northern China

Luo, Bing; Tang, Xiuming; Jia, Yuping; Wang, Yun; Yan, Chao; Zhao, Chengquan

doi:10.1016/j.micinf.2011.04.002

Cited by 12 publications

(23 citation statements)

References 44 publications

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“…Meanwhile, only 1/89 samples presented this variant in Asia . On the other hand, variant BZLF1‐A2, which was not associated with nasopharyngeal or gastric carcinomas in Asia , was statistically associated with lymphomas in our region. Moreover, the presence of a 29‐bp unit internal repeat, instead of a 30‐bp unit repeat, was also associated with lymphomas and in turn with BZLF1‐A2 variant.…”

Section: Discussionmentioning

confidence: 58%

“…Prototype sequences for each BZLF1 variant ( Z ta‐ A 1, A 2, B 1 to B 5 and Z ta‐ C ) were characterized in ref. . Bootstrap values obtained after 1000 resamplings are indicated.…”

Section: Resultsmentioning

confidence: 99%

“…Based on phylogenetic analysis and following the terminology introduced by Luo et al . , we characterized sequence variation in the coding region of the BZLF1 gene in IM and lymphoma patients from our geographic region as representatives of the lytic and latent EBV states, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

Lorenzetti

Gantuz

Altcheh

et al. 2014

Clinical Microbiology and Infection

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The ubiquitous Epstein-Barr virus (EBV) is related to the development of several lymphoid and epithelial malignancies and is also the aetiological agent for infectious mononucleosis (IM). BZLF1, an immediate early gene, plays a key role in modulating the switch from latency to lytic replication, hence enabling viral propagation. Polymorphic variations in the coded protein have been studied in other geographical regions in a search for viral factors that are inherent to malignancies and differ from those present in benign infections. In the present study, in samples of paediatric patients with benign IM and paediatric patients with malignant lymphomas, we detected previously described sequence variations as well as distinctive sequence polymorphisms from our region. By means of phylogenetic reconstruction, we characterized new phylogenetically distinct variants. Moreover, we described an association between specific variants and the studied pathologies in our region, particularly variant BZLF1-A2 with lymphomas and BZLF1-C with IM. Additionally, length polymorphisms within intron 1 were also assessed and compared between pathologies resulting in an association between 29-bp repeated units and lymphomas. In conclusion, this is the first report to characterize BZLF1 gene polymorphisms in paediatric patients from our geographical region and to suggest the association of these polymorphisms with malignant lymphomas.

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Section: Discussionmentioning

confidence: 58%

“…Prototype sequences for each BZLF1 variant ( Z ta‐ A 1, A 2, B 1 to B 5 and Z ta‐ C ) were characterized in ref. . Bootstrap values obtained after 1000 resamplings are indicated.…”

Section: Resultsmentioning

confidence: 99%

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Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

Lorenzetti

Gantuz

Altcheh

et al. 2014

Clinical Microbiology and Infection

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“…The BZLF1 promoter has also been investigated in detail in an attempt to understand why some EBV isolates supported lytic replication more efficiently than others and gave rise to the current recognition of 5 variants (Zp-P, Zp-PV, Zp-V1, Zp-V3, and Zp-V4) that are themselves subdivided into multiple subvariants (Chang et al 2009;Gutierrez et al 2002;Tong et al 2003;Martini et al 2007;Lorenzetti et al 2009;Jin et al 2010;Yu et al 2012;Lorenzetti et al 2012). BZLF1 proteins have been subdivided into groups A1, A2, B1, B2, B3, B4, B5, B6, C, D, E, F, some of which such as A1, A2, and C also contain variants (Chang et al 2009;Luo et al 2011;Lorenzetti et al 2014). There is growing evidence that some BZLF1 variants are endowed with different properties in recombinant viruses (Tsai et al 2013, see paragraph 8).…”

Section: The Degree Of Protein Heterogeneity Varies Among Viral Proteinsmentioning

confidence: 99%

Epstein–Barr Virus: From the Detection of Sequence Polymorphisms to the Recognition of Viral Types

Feederle

Klinke

Kutikhin

et al. 2015

Current Topics in Microbiology and Immunology

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The Epstein-Barr virus is etiologically linked with the development of benign and malignant diseases, characterized by their diversity and a heterogeneous geographic distribution across the world. The virus possesses a 170-kb-large genome that encodes for multiple proteins and non-coding RNAs. Early on there have been numerous attempts to link particular diseases with particular EBV strains, or at least with viral genetic polymorphisms. This has given rise to a wealth of information whose value has been difficult to evaluate for at least four reasons. First, most studies have looked only at one particular gene and missed the global picture. Second, they usually have not studied sufficient numbers of diseased and control cases to reach robust statistical significance. Third, the functional significance of most polymorphisms has remained unclear, although there are exceptions such as the 30-bp deletion in LMP1. Fourth, different biological properties of the virus do not necessarily equate with a different pathogenicity. This was best illustrated by the type 1 and type 2 viruses that markedly differ in terms of their transformation abilities, yet do not seem to cause different diseases. Reciprocally, environmental and genetic factors in the host are likely to influence the outcome of infections with the same virus type. However, with recent developments in recombinant virus technology and in the availability of high throughput sequencing, the tide is now turning. The availability of 23 complete or nearly complete genomes has led to the recognition of viral subtypes, some of which possess nearly identical genotypes. Furthermore, there is growing evidence that some genetic polymorphisms among EBV strains markedly influence the biological and clinical behavior of the virus. Some virus strains are endowed with biological properties that explain crucial clinical features of patients with EBV-associated diseases. Although we now have a better overview of the genetic diversity within EBV genomes, it has also become clear that defining phenotypic traits evinced by cells infected by different viruses usually result from the combination of multiple polymorphisms that will be difficult to identify in their entirety. However, the steadily increasing number of sequenced EBV genomes and cloned EBV BACS from diseased and healthy patients will facilitate the identification of the key polymorphisms that condition the biological and clinical behavior of the viruses. This will allow the development of preventative and therapeutic approaches against highly pathogenic viral strains.

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“…Natural variation in the BZLF1 protein sequence has been described in Chinese isolates but showed no relationship to disease (Ji et al 2008;Luo et al 2011). Variation in the BZLF1 dimerisation sequence was studied using synthetic peptides but found to have only a small effect on its activity (Hicks et al 2001).…”

Section: Lytic Cyclementioning

confidence: 99%

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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Sequence variation of Epstein-Barr virus (EBV) BZLF1 gene in EBV-associated gastric carcinomas and nasopharyngeal carcinomas in Northern China

Cited by 12 publications

References 44 publications

Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

Epstein–Barr virus BZLF1 gene polymorphisms: malignancy related or geographically distributed variants?

Epstein–Barr Virus: From the Detection of Sequence Polymorphisms to the Recognition of Viral Types

Epstein–Barr Virus Strain Variation

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