Alterations in critical cellular pathways during lytic Epstein-Barr Virus infection

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Dana A. Jeffus (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Amy Adamson

Abstract: Epstein-Barr Virus (EBV) is a human herpesvirus that infects approximately 90% of the global human population. Infection with EBV is associated with several diseases, such as Burkitt’s Lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. In both latent and lytic states, EBV produces gene products that interfere with normal host cell signaling mechanisms. Promoter regions within the EBV genome contain binding sites for a variety of cellular transcription factors. EBV also lacks the machinery necessary for synthesis of viral proteins, and therefore must exploit major cell signaling pathways for cap-dependent translation. The PI3K–Akt–mTOR and MAPK pathways stimulate downstream targets to promote biogenesis. EBV interaction with proteins in these pathways can result in uncontrolled cell growth, proliferation, and apoptosis resistance, potentially leading to carcinogenesis. Previous research shows that under rapamycin-induced inhibition of mTORC1, a major component of PI3K–Akt–mTOR pathway, EBV lytic protein production varies in a cell-type specific manner, suggesting that EBV utilizes these pathways differently among B cells and epithelial cells. For this study, I investigated the molecular targets of EBV within these pathways to gain further insight into the mechanisms involved in synthesis of EBV lytic gene products. The results show that EBV activates variable levels of proteins within the PI3K–Akt–mTOR and MAPK pathways in different cell types during lytic replication, the MAPK pathways are used as a major alternative pathway when mTORC1 is inhibited, and inhibition of the mTOR and MAPK pathways utilized by EBV does not attenuate viral replication.

Additional Information

Language: English
Date: 2018
EBV, Epstein-Barr Virus, Lytic, MAPK, mTOR, Protein
Epstein-Barr virus
Epstein-Barr virus diseases
Protein kinases
Viral proteins

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