Epstein-Barr Virus Nuclear Antigen 3A Promotes Cellular Proliferation by Repression of the Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1


Epstein-Barr virus (EBV) infects over 98% of the population worldwide and is associated with a variety of human cancers. In the healthy host, the virus represses expression of its proteins to avoid detection by the immune system to enable it to remain in the body for the lifetime of its host, a situation known as latency. This downregulation was first observed in EBV-associated Burkitt lymphoma (BL), which classically express only one viral protein, EBNA-1. A subset of BL named Wp-restricted (Wp-R) BL express additional latency-associated viral proteins. Because Wp-R BL also express wild-type p53 (which normally prevents cellular proliferation), we wanted to explore the possibility that these viral proteins play a role in tumorigenesis. Indeed, we have demonstrated that Wp-R BL cells are more tumorigenic in immunocompromised mice than other BL. Here, we have investigated the role of one of these viral proteins, EBNA-3A. If we inhibit the expression of EBNA-3A, Wp-R BL cells fail to proliferate and express increased p21WAF1/CIP1, a cellular protein that inhibits cell proliferation. These results suggest that this previously undescribed function of EBNA-3A plays a role in the proliferation and likely contributes to tumorigenesis in Wp-R BL.


Vyšlo v časopise: Epstein-Barr Virus Nuclear Antigen 3A Promotes Cellular Proliferation by Repression of the Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004415
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1004415

Souhrn

Epstein-Barr virus (EBV) infects over 98% of the population worldwide and is associated with a variety of human cancers. In the healthy host, the virus represses expression of its proteins to avoid detection by the immune system to enable it to remain in the body for the lifetime of its host, a situation known as latency. This downregulation was first observed in EBV-associated Burkitt lymphoma (BL), which classically express only one viral protein, EBNA-1. A subset of BL named Wp-restricted (Wp-R) BL express additional latency-associated viral proteins. Because Wp-R BL also express wild-type p53 (which normally prevents cellular proliferation), we wanted to explore the possibility that these viral proteins play a role in tumorigenesis. Indeed, we have demonstrated that Wp-R BL cells are more tumorigenic in immunocompromised mice than other BL. Here, we have investigated the role of one of these viral proteins, EBNA-3A. If we inhibit the expression of EBNA-3A, Wp-R BL cells fail to proliferate and express increased p21WAF1/CIP1, a cellular protein that inhibits cell proliferation. These results suggest that this previously undescribed function of EBNA-3A plays a role in the proliferation and likely contributes to tumorigenesis in Wp-R BL.


Zdroje

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