Do Epstein–Barr Virus Mutations and Natural Genome Sequence Variations Contribute to Disease?

Farrell, Patrick J.; White, Rob

doi:10.3390/biom12010017

Cited by 20 publications

(18 citation statements)

References 64 publications

(95 reference statements)

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“…The 172-nt sequence of EBER2 is generally well-conserved among EBV strains recovered from B cell lymphomas and lymphoma-derived B cell lines. However, it was reported recently that some EBV strains, including strain M81, which displays differential association with nasopharyngeal carcinoma ( 14 , 15 ), carry EBER2 single nucleotide polymorphisms (SNPs) that may contribute to the virus life cycle ( 16 – 19 ). Included among the M81 EBER2 SNPs are nucleotides at positions 44, 46, 57, 61, 93, 168, and 170 that are present in M81 and many EBV strains from China but differ from the nucleotides that are conserved among most EBV strains from other parts of the world ( 14 , 15 ), including the B95-8 EBER2 expressed by the ΔT4.E2.b virus.…”

Section: Observationmentioning

confidence: 99%

A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells

Wang

Ungerleider

Hoffman

et al. 2022

mBio

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The oncogenic gammaherpesviruses, including human Epstein-Barr virus (EBV), human Kaposi’s sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, γHV68, MuHV-4), are associated with numerous malignancies, including B cell lymphomas and nasopharyngeal carcinoma. These viruses employ numerous molecular strategies to colonize the host, including the expression of noncoding RNAs (ncRNAs). As the first viral ncRNAs identified, EBV-encoded RNA 1 and 2 (EBER1 and EBER2, respectively) have been investigated extensively for decades; however, their specific in vivo functions remain largely unknown.

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Section: Observationmentioning

confidence: 99%

A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells

Wang

Ungerleider

Hoffman

et al. 2022

mBio

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“…The development of high‐throughput sequencing technologies has enabled sequencing of EBV genomes derived from a wide variety of clinical samples. In addition, the sequences of EBV genes/genomes vary geographically, and several geographically specific high‐risk EBV subtypes for NPC or other tumors have been identified 11–16 . Recently, studies from NPC‐endemic China have shown that two single‐nucleotide polymorphisms (SNPs) of BALF2, T162476C and C163364T, are associated with risk of NPC 16 …”

Section: Introductionmentioning

confidence: 99%

“…In addition, the sequences of EBV genes/genomes vary geographically, and several geographically specific high-risk EBV subtypes for NPC or other tumors have been identified. [11][12][13][14][15][16] Recently, studies from NPCendemic China have shown that two single-nucleotide polymorphisms (SNPs) of BALF2, T162476C and C163364T, are associated with risk of NPC. 16 EBV was the first human virus shown to encode microRNAs (miRNAs).…”

Section: Introductionmentioning

confidence: 99%

BART‐D2 subtype of EBV encoded BART miRNA cluster 1 region is strongly associated with endemic nasopharyngeal carcinoma

Wang

He²,

et al. 2023

Journal of Medical Virology

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Epstein-Barr virus (EBV)-encodedBamHI A rightward transcript (BART) microRNAs (miRNAs) play important roles in viral infection and tumorigenesis. The association of sequence variations in the BART miRNA cluster 1 region with diseases remains unclear. Herein, 6 types and 11 subtypes of BART cluster 1 were identified in 354 tumors and healthy donors (HDs) from nasopharyngeal carcinoma (NPC)-endemic and nonendemic China (genotyped data), and 905 EBV genomes retrieved from GenBank from diseased and normal people from around the world (archived data). The distributions of BART cluster 1 types/subtypes between NPC-endemic and nonendemic China; between Asian regions and Africa/Europe & Australia & United States; and among Asian regions (NPC-endemic China, NPC-nonendemic East Asia and Southeast Asia) were significantly different (p < 0.001). The subtype BART-D2was not found outside Asia and was only common in NPC-endemic China. More importantly, BART-D2 had a higher frequency in NPCs than in HDs in NPC-endemic China (genotyped data, 78.0% vs. 44.1%, p < 0.001; achieved data, 89.3% vs. 43.7%, p < 0.001), and was also more frequent in NPCs than in HDs, gastric carcinomas, and lymphomas in NPC-nonendemic China (genotyped data, 27.9% vs. 1.9%, 2.4%, and 0.0%, p < 0.001). BART-D2 was preferentially linked with the high-risk subtypes for NPC previously reported, 162476C or 163364T, in the BALF2 gene, and was associated with NPC risk (p < 0.01). In vitro experiments showed that BART-D2 affected the expression of some mature BART miRNAs. These findings demonstrate geographically restricted variations of BART cluster 1 and identify distinct subtype that is confined to NPC-endemic China and is associated with NPC.

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“…However almost nothing is known about differences between T1 and T2 EBV infection in epithelial cells. T1 EBV infection is much more common than T2 EBV infection in western countries [30] and most previous studies in the EBV field have been performed using T1 EBV strains. T2 EBV infection has been reported to be present in up to 50% of the population in sub-Saharan Africa and New Guinea [15][16][17][18][19][20][21][22], and humans can be simultaneously infected with both types [21,22].…”

Section: Introductionmentioning

confidence: 99%

Type 1 and Type 2 Epstein-Barr viruses induce proliferation, and inhibit differentiation, in infected telomerase-immortalized normal oral keratinocytes

et al. 2022

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Differentiated epithelial cells are an important source of infectious EBV virions in human saliva, and latent Epstein-Barr virus (EBV) infection is strongly associated with the epithelial cell tumor, nasopharyngeal carcinoma (NPC). However, it has been difficult to model how EBV contributes to NPC, since EBV has not been shown to enhance proliferation of epithelial cells in monolayer culture in vitro and is not stably maintained in epithelial cells without antibiotic selection. In addition, although there are two major types of EBV (type 1 (T1) and type 2 (T2)), it is currently unknown whether T1 and T2 EBV behave differently in epithelial cells. Here we inserted a G418 resistance gene into the T2 EBV strain, AG876, allowing us to compare the phenotypes of T1 Akata virus versus T2 AG876 virus in a telomerase-immortalized normal oral keratinocyte cell line (NOKs) using a variety of different methods, including RNA-seq analysis, proliferation assays, immunoblot analyses, and air-liquid interface culture. We show that both T1 Akata virus infection and T2 AG876 virus infection of NOKs induce cellular proliferation, and inhibit spontaneous differentiation, in comparison to the uninfected cells when cells are grown without supplemental growth factors in monolayer culture. T1 EBV and T2 EBV also have a similar ability to induce epithelial-to-mesenchymal (EMT) transition and activate canonical and non-canonical NF-κB signaling in infected NOKs. In contrast to our recent results in EBV-infected lymphoblastoid cells (in which T2 EBV infection is much more lytic than T1 EBV infection), we find that NOKs infected with T1 and T2 EBV respond similarly to lytic inducing agents such as TPA treatment or differentiation. These results suggest that T1 and T2 EBV have similar phenotypes in infected epithelial cells, with both EBV types enhancing cellular proliferation and inhibiting differentiation when growth factors are limiting.

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Do Epstein–Barr Virus Mutations and Natural Genome Sequence Variations Contribute to Disease?

Cited by 20 publications

References 64 publications

A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells

A Polymorphism in the Epstein-Barr Virus EBER2 Noncoding RNA Drives In Vivo Expansion of Latently Infected B Cells

BART‐D2 subtype of EBV encoded BART miRNA cluster 1 region is strongly associated with endemic nasopharyngeal carcinoma

Type 1 and Type 2 Epstein-Barr viruses induce proliferation, and inhibit differentiation, in infected telomerase-immortalized normal oral keratinocytes

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