Genome-Wide Analysis of 18 Epstein-Barr Viruses Isolated from Primary Nasopharyngeal Carcinoma Biopsy Specimens

Abstract

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that is highly prevalent in almost all human populations and is associated with many human cancers, such as nasopharyngeal carcinoma (NPC), Hodgkin's disease, and gastric carcinoma. However, in these EBV-associated cancers, only NPC exhibits remarkable ethnic and geographic distribution. We hypothesized that EBV genomic variations might contribute to the pathogenesis of different human cancers in different geographic areas. In this study, we collected 18 NPC biopsy specimens from the Hunan Province in southern China and assembled 18 NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HN1 to HN18. This was achieved through target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, to reveal sequence diversity. These EBV genomes harbored 20,570 variations totally, including 20,328 substitutions, 88 insertions, and 154 deletions, compared to the EBV reference genome. Phylogenetic analysis revealed that all NPC-EBV genomes were distinct from other EBV genomes. Furthermore, HN1 to HN18 had some nonsynonymous variations in EBV genes including genes encoding latent, early lytic, and tegument proteins, such as substitutions within transmembrane domains 1 and 3 of LMP1, FoP_duplication, and zf-AD domains of ENBA1, in addition to aberrations in noncoding regions, especially in BamHI A rightward transcript microRNAs. These variations might have potential biological significance. In conclusion, we reported a genome-wide view of sequence variation in EBV isolated from primary NPC biopsy specimens obtained from the Hunan Province. This might contribute to further understanding of how genomic variations contribute to carcinogenesis, which would impact the treatment of EBV-associated cancer. Nasopharyngeal carcinoma (NPC) is highly associated with Epstein-Barr virus (EBV) infection and exhibits remarkable ethnic and geographic distribution. Hunan Province in southern China has a high incidence rate of NPCs. Here, we report 18 novel EBV genome sequences from viruses isolated from primary NPC biopsy specimens in this region, revealing whole-genome sequence diversity.

circMAN1A2 could serve as a novel serum biomarker for malignant tumors

“…For example, plasma lipocalin‐2 is upregulated in pediatric thyroid cancer and could have applications as a new biomarker . Serum lactate dehydrogenase has also been shown to act as a significant marker of head and neck squamous cell carcinoma, and Epstein‐Barr virus (EBV) DNAs or miRNAs are significantly correlated with distant metastasis and death in patients with NPC . Serum hsa‐miR‐1273 g‐3p might also have potential applications as both a prognostic and diagnostic biomarker of recurrent epithelial ovarian cancer .…”

“…10 Serum lactate dehydrogenase has also been shown to act as a significant marker of head and neck squamous cell carcinoma, 11 and Epstein-Barr virus (EBV) DNAs or miRNAs are significantly correlated with distant metastasis and death in patients with NPC. [12][13][14][15][16][17][18] Serum hsa-miR-1273 g-3p might also have potential applications as both a prognostic and diagnostic biomarker of recurrent epithelial ovarian cancer. 19 Squamous cell carcinoma antigen, a marker of squamous cell carcinoma, can be used to detect head and neck cancers.…”

Epstein-Barr Virus Nuclear Antigen 1 Recruits Cyclophilin A to Facilitate the Replication of Viral DNA Genome

“…EBV ubiquitously infects more than 90% of the global population and is closely associated with the development of several malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) (Shair et al, 2008;Yu et al, 2012;Young, 2014;Young and Dawson, 2014;Liu et al, 2017). NPC, which is primarily of epithelial origin, is a type of metastatic head-and-neck neoplasm that is highly prevalent in southern China and some other areas in East Asia and Africa (Tang et al, 2016;Tu et al, 2017;Jiang et al, 2018).…”

Epstein-Barr Virus miR-BART6-3p Inhibits the RIG-I Pathway

“…Transcription of its genome varies from different states of infection [13] . EBV has developed multiple strategies to evade the host's antiviral response.…”