Epstein Barr Virus Encoded MicroRNAs Impact Proliferation and Autophagy in Transfected Cells in vitro
Barr Virus infects greater than 95% of the adult population and remains latent in memory
B cells for the life of the host. EBV is associated with a number of cancers including
Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), Hodgkin
Lymphoma (HL) and others. Investigations into the causes of this association are
necessary to improve outcomes f... read moreor patients. The EBV viral genome encodes a number of
genes that are transcribed during the course on infection, including proteins and
microRNAs. Each transcription program is associated with a different stage in B cell
differentiation, for example Latency III during the activated lymphoblast stage, Latency
II during germinal center differentiation, and Latency I/0 during memory. EBV associated
cancers can be characterized based on the infection stage of the cells they arose from.
For example, NPC is Latency II, while BL is Latency I. Of the EBV encoded microRNAs, a
subset of BARTs are only expressed during the proliferative Latency III phase, and are
also found to be expressed in EBV associated cancers that otherwise characterized as EBV
Latency II or I/0 cancers. Therefore, these microRNAs are expressed during rapid
proliferation and are dysregulated in tumor samples, suggesting there may be a link
between tumorigenesis and expression of this subset of microRNAs due to their common
expression during period of cell cycle disregulation. Thus, I aimed to further elucidate
the role of one or more BART microRNAs that are highly expressed during Latency III as
well as in a number of EBV associated tumor samples. I sought to characterize the impact
on host cell processes, including proliferation, growth, and survival. I was able to
identify and validate a target for miR-BART10, ATP6V0e, which encodes a subunit of a
V-Type ATPase that is involved in pH maintenance and autophagy. I also observed an
increase in proliferation of relevant cell lines in vitro when transfected with
miR-BART10, as well as miR-BART 14* and
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Immunology.
Advisor: David Thorley Lawson.
Committee: Alexander Poltorak, Linden Hu, and Marta Gaglia.
Keyword: Immunology.read less