The hide-and-seek game of the oncogenic Epstein-Barr virus-encoded EBNA1 protein with the immune system: An RNA G-quadruplex tale.

Autor: Dinh VT; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France. Electronic address: dinhtrangtnhp@gmail.com., Loaëc N; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France., Quillévéré A; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France., Le Sénéchal R; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France., Keruzoré M; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France., Martins RP; ISP, INRAE, Univ Tours, UMR1282, Tours, Nouzilly, France., Granzhan A; Chemistry and Modelling for the Biology of Cancer (CMBC), CNRS UMR9187, Inserm U1196, Institut Curie, Université Paris Saclay, F-91405 Orsay, France., Blondel M; Univ Brest; Inserm UMR1078; Etablissement Français Du Sang (EFS) Bretagne; CHRU Brest, Hôpital Morvan, Laboratoire de Génétique Moléculaire, 22 Avenue Camille Desmoulins, F-29200 Brest, France. Electronic address: marc.blondel@univ-brest.fr.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2023 Nov; Vol. 214 (Pt A), pp. 57-68. Date of Electronic Publication: 2023 Jul 19.
DOI: 10.1016/j.biochi.2023.07.010
Abstrakt: The Epstein-Barr virus (EBV) is the first oncogenic virus described in human. EBV infects more than 90% of the human population worldwide, but most EBV infections are asymptomatic. After the primary infection, the virus persists lifelong in the memory B cells of the infected individuals. Under certain conditions the virus can cause several human cancers, that include lymphoproliferative disorders such as Burkitt and Hodgkin lymphomas and non-lymphoid malignancies such as 100% of nasopharyngeal carcinoma and 10% of gastric cancers. Each year, about 200,000 EBV-related cancers emerge, hence accounting for at least 1% of worldwide cancers. Like all gammaherpesviruses, EBV has evolved a strategy to escape the host immune system. This strategy is mainly based on the tight control of the expression of its Epstein-Barr nuclear antigen-1 (EBNA1) protein, the EBV-encoded genome maintenance protein. Indeed, EBNA1 is essential for viral genome replication and maintenance but, at the same time, is also highly antigenic and T cells raised against EBNA1 exist in infected individuals. For this reason, EBNA1 is considered as the Achilles heel of EBV and the virus has seemingly evolved a strategy that employs the binding of nucleolin, a host cell factor, to RNA G-quadruplex (rG4) within EBNA1 mRNA to limit its expression to the minimal level required for function while minimizing immune recognition. This review recapitulates in a historical way the knowledge accumulated on EBNA1 immune evasion and discusses how this rG4-dependent mechanism can be exploited as an intervention point to unveil EBV-related cancers to the immune system.
(Copyright © 2023 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)
Databáze: MEDLINE
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