Differential Epstein Barr Virus expression in B cells and neuronal cells

Identification: Jha, Hem Chandra


Differential Epstein Barr Virus expression in B cells and neuronal cells
Shweta Jakhmola1, Dr Hem Chandra Jha1*
1Indian Institute of Technology Indore
*Corresponding Author
Worldwide clinical findings have linked EBV to neuronal pathologies, including multiple sclerosis, primary central nervous system lymphoma, and Alzheimer's disease. Initial infection of naive B cells by EBV is followed by expression of all the viral latent genes namely Epstein-Barr nuclear antigens (EBNA) 1, 2, 3A, 3B, 3C, and LP and the latent membrane proteins (LMP) 1, 2A, and 2B, that is the virus exhibits latency III or “growth” program. The B cells are then transformed to lymphoblast. The EBV latency III genes are down-regulated as the B blast enter the germinal centre. EBV latency II genes namely EBNA1, LMP1, and LMP2 are then expressed and allow the progression of the B cells through the germinal centre to become a memory B cell. These memory cells circulate in the peripheral circulatory system. During its dissemination only EBNA1 is expressed, that is EBV exhibits only phase I latency program which enables the virus to replicate. The in vitro culturing of the B cells on EBV infection displays similar pattern of EBV phase transition that is from latency III to latency II followed by latency I gene expression. Moreover, according to a hypothesis, in case of MS, the EBV infected B cells demonstrate EBNA1, LMP1, and LMP2 latency II gene expression pattern. However, in clinical studies of CSF of MS patients only EBNA1 is analysed, suggesting that only latency I of EBV is active. Our study has demonstrated gammaherpesvirus infection of neuronal cells. In this study, for the first time, we have successfully demonstrated the in vitro infection of Sh-Sy5y and Ntera2 cells, as well as human primary neurons. In vitro neuronal infection by EBV displays that the virus follows latency I to establish infection.  Epstein-Barr nuclear antigens (EBNA) 1, 2, 3A, 3B, 3C are clearly established in EBV infected neuronal cells. These findings may open new avenues of consideration related to neuronal pathologies and infection with EBV. Furthermore, to understand the differences between B cells and neuronal cells infection through EBV, in which the expression pattern of latent antigens are different, is crucial to explore. Also, how the host environment in neuronal infection is different and contributing in disease pathogenesis compared to B cells is important to reveal. Also, their contribution to chronic infection linked to neuronal disease will provide new clues to potential new therapies.


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