Next Article in Journal
Shedding Light on the African Enigma: In Vitro Testing of Homo sapiens-Helicobacter pylori Coevolution
Previous Article in Journal
Quorum Sensing Regulation in Phytopathogenic Bacteria
Previous Article in Special Issue
Epstein–Barr Virus Reactivation-Induced Immunoglobulin Production: Significance on Autoimmunity
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Editorial

Special Issue: Epstein–Barr–Virus–Associated Cancers

Research Center for the Control and Prevention of Infectious Diseases, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan
Microorganisms 2021, 9(2), 241; https://doi.org/10.3390/microorganisms9020241
Submission received: 8 January 2021 / Accepted: 21 January 2021 / Published: 25 January 2021
(This article belongs to the Special Issue Epstein–Barr Virus Infection and Associated Diseases)
Epstein–Barr virus (EBV), a ubiquitous human gamma herpesvirus, infects a majority of the population worldwide (~95%). Although EBV infections are persistent and lifelong, they are largely asymptomatic. However, the virus can cause various lymphoid and epithelial malignancies, such as Burkitt’s lymphoma, Hodgkin lymphoma (HL), gastric carcinoma (GC), and nasopharyngeal carcinoma (NPC). Since its discovery as the first human oncovirus in 1964, accumulating evidence indicates that a variety of viral factors, including oncoproteins and non-coding RNAs, contribute to the development of EBV-associated cancers by regulating diverse cellular machineries [1]. Despite extensive research, the underlying mechanisms by which EBV causes cancers in only a restricted population remains unclear.
This Special Issue assembles eleven papers, comprising seven research articles, two reviews, and two brief reports, which collectively provide novel information on the mechanisms of oncogenesis [2,3,4,5,6] and viral replication [7,8,9,10], as well as applications for diagnosis [11,12].
Using a variety of methods and approaches, several studies have provided a novel notion in understanding how EBV contributes to the development of various tumors, including GC [2,3], HL [4], NPC [5], and oral squamous cell carcinoma [6], on a molecular basis. A distinct feature of EBV-associated GC is the significant infiltration of immune cells in the epithelium, which appears to establish a unique tumor microenvironment. A study demonstrated that exosomes induce the suppression of maturation of infiltrated dendritic cells in EBV-associated GC [2]. Bioinformatic approaches revealed that an EBV-encoded microRNA, miR-BART17-5p, directly downregulates Kruppel-like factor 2 in EBV-associated GC cells, which subsequently confers an oncogenic phenotype [3]. Other studies identified host factors such as Notch1 and Pax5 or Semaphorin 3A, which exhibited correlated expression with viral infection in EBV-associated HL [4] or NPC [5], respectively, indicating that they could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in these tumors. EBV establishes latent infection in squamous cell carcinoma cell lines, suggesting that it can be used as an in vitro model to investigate the role of EBV in the development of uncharacterized oral squamous cell carcinoma [6].
Some studies have broadened our knowledge of the maturation of EBV particles. One study characterized the role of EBV-encoded BBRF2 in the viral lytic cycle by using a knockout virus. Although the viral gene expression, genome propagation, and progeny production were not affected by deletion of the BBRF2 gene, infectivity of the progeny viruses was reduced. Further analysis demonstrated that BBRF2 protects its counter partner, BSRF1, from proteasome/ubiquitin-mediated degradation [7]. Another study using microscopic approaches provided further insights into the EBV lifecycle by demonstrating that EBV exploits the host secretion pathway for the release of progeny virions into the extracellular milieu [8].
Furthermore, two studies introduced novel approaches for the diagnosis of EBV-associated GC. The contribution of Helicobacter pylori-induced persistent gastric mucosal ulceration damage in EBV-associated GC was evaluated using the rapid urease test to measure viral copy numbers in gastric biopsy samples with atrophic gastritis. A significant correlation was found between high viral copy numbers and severe grades of atrophic gastritis [11]. A droplet digital PCR-based screening method was established to assess the EBV infection status in the GC specimens, which was validated through complete correlation with a conventional EBER1 in situ hybridization assay [12].
Finally, the two reviews highlight the contribution of the viral lytic cycle in EBV-associated diseases. One provides recent knowledge about EBV-induced autoimmune diseases, which is likely mediated by the upregulation of antibody secretion from latently infected B cells upon EBV reactivation [9]. The second is a systematic review discussing the recent advances in understanding the molecular mechanism by which lytic cycle of EBV contributes to tumor formation and progression [10].
Collectively, this Special Issue presents significant progress in the understanding of how EBV induces oncogenesis in various ways; nevertheless, the fundamental priority is yet to be addressed. Further studies are necessary to enable the development of therapeutics to control EBV-associated diseases.

Funding

This research received no external funding.

Acknowledgments

I would like to thank all authors and the reviewers for contribution to this Special Issue. I would also like to express my appreciation for the continuous support from the Microorganisms editorial office.

Conflicts of Interest

The author declares no conflict of interest.

References

  1. Longnecker, R.M.; Kieff, E.; Cohen, J.I. Epstein-Barr Virus. In Fields Virology, 6th ed.; Knipe, M., Howley, P.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2013; pp. 1898–1959. [Google Scholar]
  2. Hinata, M.; Kunita, A.; Abe, H.; Morishita, Y.; Sakuma, K.; Yamashita, H.; Seto, Y.; Ushiku, T.; Fukayama, M. Exosomes of epstein-barr virus-associated gastric carcinoma suppress dendritic cell maturation. Microorganisms 2020, 8, 1776. [Google Scholar] [CrossRef]
  3. Yoon, J.H.; Min, K.; Lee, S.K. Epstein-barr virus mir-bart17-5p promotes migration and anchorage-independent growth by targeting kruppel-like factor 2 in gastric cancer. Microorganisms 2020, 8, 258. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Palma-Lara, I.; Sanchez-Aldana, A.E.; Jimenez-Hernandez, E.; Martinez-Villegas, O.; Nunez-Enriquez, J.C.; Mejia-Arangure, J.M.; Ochoa, S.A.; Xicohtencatl-Cortes, J.; Cruz-Cordova, A.; Zavala-Vega, S.; et al. Variable expression of notch1 and pax5 in classical hodgkin lymphoma and infection with epstein-barr in pediatric patients. Microorganisms 2020, 8, 958. [Google Scholar] [CrossRef]
  5. Imoto, T.; Kondo, S.; Wakisaka, N.; Hai, P.T.; Seishima, N.; Kano, M.; Ueno, T.; Mizokami, H.; Nakanishi, Y.; Hatano, M.; et al. Overexpression of semaphorin 3a is a marker associated with poor prognosis in patients with nasopharyngeal carcinoma. Microorganisms 2020, 8, 423. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  6. Heawchaiyaphum, C.; Iizasa, H.; Ekalaksananan, T.; Burassakarn, A.; Kiyono, T.; Kanehiro, Y.; Yoshiyama, H.; Pientong, C. Epstein-barr virus infection of oral squamous cells. Microorganisms 2020, 8, 419. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  7. Masud, H.; Yanagi, Y.; Watanabe, T.; Sato, Y.; Kimura, H.; Murata, T. Epstein-barr virus bbrf2 is required for maximum infectivity. Microorganisms 2019, 7, 705. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  8. Nanbo, A. Epstein-barr virus exploits the secretory pathway to release virions. Microorganisms 2020, 8, 729. [Google Scholar] [CrossRef] [PubMed]
  9. Nagata, K.; Hayashi, K. Epstein-barr virus reactivation-induced immunoglobulin production: Significance on autoimmunity. Microorganisms 2020, 8, 1875. [Google Scholar] [CrossRef] [PubMed]
  10. Rosemarie, Q.; Sugden, B. Epstein-barr virus: How its lytic phase contributes to oncogenesis. Microorganisms 2020, 8, 1824. [Google Scholar] [CrossRef] [PubMed]
  11. Kartika, A.V.; Iizasa, H.; Ding, D.; Kanehiro, Y.; Tajima, Y.; Kaji, S.; Yanai, H.; Yoshiyama, H. Application of biopsy samples used for helicobacter pylori urease test to predict epstein-barr virus-associated cancer. Microorganisms 2020, 8, 923. [Google Scholar] [CrossRef] [PubMed]
  12. Shuto, T.; Nishikawa, J.; Shimokuri, K.; Yanagi, A.; Takagi, T.; Takagi, F.; Miura, O.; Iida, M.; Nagano, H.; Takemoto, Y.; et al. Establishment of a screening method for epstein-barr virus-associated gastric carcinoma by droplet digital pcr. Microorganisms 2019, 7, 628. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Nanbo, A. Special Issue: Epstein–Barr–Virus–Associated Cancers. Microorganisms 2021, 9, 241. https://doi.org/10.3390/microorganisms9020241

AMA Style

Nanbo A. Special Issue: Epstein–Barr–Virus–Associated Cancers. Microorganisms. 2021; 9(2):241. https://doi.org/10.3390/microorganisms9020241

Chicago/Turabian Style

Nanbo, Asuka. 2021. "Special Issue: Epstein–Barr–Virus–Associated Cancers" Microorganisms 9, no. 2: 241. https://doi.org/10.3390/microorganisms9020241

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop